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Oligomerization is a core structural feature that defines the form and function of many proteins. Most proteins form molecular complexes; however, there remains a dearth of diversity-driven structural studies investigating the evolutionary trajectory of these assemblies. Ribulose-1,5-bisphosphate carboxylase-oxygenase (RuBisCO) is one such enzyme that adopts multiple assemblies, although the origins and distribution of its different oligomeric states remain cryptic. Here, we retrace the evolution of ancestral and extant form II RuBisCOs, revealing a complex and diverse history of oligomerization. We structurally characterize a newly discovered tetrameric RuBisCO, elucidating how solvent-exposed surfaces can readily adopt new interactions to interconvert or give rise to new oligomeric states. We further use these principles to engineer and demonstrate how changes in oligomerization can be mediated by relatively few mutations. Our findings yield insight into how structural plasticity may give rise to new oligomeric states.

The loess–palaeosol sequence and intercalated Palaeolithic find layers at the former brickyard of Rheindahlen are matters of ongoing scientific dispute. The age of different palaeosols and loess layers, hence their correlation with the global climate cycles, and the timing of repeated Neanderthal occupations have been hotly debated. These disagreements should be solved because the exceptional sedimentary and Palaeolithic sequences at Rheindahlen provide a unique opportunity to study diachronic changes in Neanderthal behaviour within the context of past climate change. We thus revisited one of the key loess sections of the Rheindahlen site to improve our understanding of loess formation processes and provide a more reliable chronostratigraphic framework for the sequence. High-resolution grain size analyses and micromorphology show that the Erkelenz Soil and the Rheindahlen Soil are characterized by more strongly developed Bt horizons than the modern soil. While these soils represent interglacial phases, the lowermost palaeosol likely formed during an interstadial and has been overprinted by weak clay illuviation during the formation of the Rheindahlen Soil. Sedimentary features of prolonged frost characterize loess and palaeosols below the modern soil and give indirect evidence for a Holocene age of the uppermost part of the sequence. Our luminescence dating approach corroborates this correlation and adds several Last Glacial deposition ages for the upper metres of the sequence. Previous correlation of this part of the sedimentary sequence with the penultimate glacial is thus rejected, whereas placing the Middle Palaeolithic inventories A3, B1, and B2 into the Last Glacial is confirmed. Luminescence measurements for the parental loess of the Erkelenz Soil and for loess layers below did not provide reliable ages probably related to signal saturation. The age of this part of the sequence thus remains open, hence the timing of human occupation testified by Palaeolithic inventories B3, B4/5, C1, and D1. The new findings provide an improved base for stratigraphic correlation of the Rheindahlen loess sequence and for investigating diachronic change in Neanderthal behaviour against the background of past climate change.

​​​​​​​Micromorphological analysis using a petrographic microscope is one of the conventional methods to characterise microfacies in rocks (sediments) and soils. This analysis of the composition and structure observed in thin sections (TSs) yields seminal, but primarily qualitative, insights into their formation. In this context, the following question arises: how can micromorphological features be measured, classified, and particularly quantified to enable comparisons beyond the micro scale? With the Micromorphological Geographic Information System (MiGIS), we have developed a Python-based toolbox for the open-source software QGIS 3, which offers a straightforward solution to digitally analyse micromorphological features in TSs. By using a flatbed scanner and (polarisation) film, high-resolution red–green–blue (RGB) images can be captured in transmitted light (TL), cross-polarised light (XPL), and reflected light (RL) mode. Merging these images in a multi-RGB raster, feature-specific image information (e.g. light refraction properties of minerals) can be combined in one data set. This provides the basis for image classification with MiGIS. The MiGIS classification module uses the random forest algorithm and facilitates a semi-supervised (based on training areas) classification of the feature-specific colour values (multi-RGB signatures). The resulting classification map shows the spatial distribution of thin section features and enables the quantification of groundmass, pore space, minerals, or pedofeatures, such nodules being dominated by iron oxide and clay coatings. We demonstrate the advantages and limitations of the method using TSs from a loess–palaeosol sequence in Rheindahlen (Germany), which was previously studied using conventional micromorphological techniques. Given the high colour variance within the feature classes, MiGIS appears well-suited for these samples, enabling the generation of accurate TS feature maps. Nevertheless, the classification accuracy can vary due to the TS quality and the academic training level, in micromorphology and in terms of the classification process, when creating the training data. However, MiGIS offers the advantage of quantifying micromorphological features and analysing their spatial distribution for entire TSs. This facilitates reproducibility, visualisation of spatial relationships, and statistical comparisons of composition among distinct samples (e.g. related sediment layers).

Abstract An adult domestic short‐haired feline leukemia virus‐infected cat was referred for kidney failure and worsening anemia requiring transfusions. ABC blood typing was performed with an immunochromatographic strip assay at different occasions. Gel column systems were used for the major and minor crossmatching tests, and anti‐A and anti‐B titers were determined. No discrete A or B bands appeared on the immunochromatographic strips at any time point for the recipient cat. The recipient's plasma agglutinated RBCs from tested type A and B cats. The recipient's RBCs appeared compatible with plasma from 1 type A and 2 B donors, and incompatible with plasma from another type A cat. Genotyping of recipient blood revealed a single homozygous c.179G>T CMAH variant predicting a blood type B. These studies suggest an unusual weak type B or missing all ABC antigens. The latter resembles the exceedingly rare Bombay phenotype in the human ABO blood group system.

Dyserythropoietic anemia and myopathy syndrome (DAMS) with neonatal losses was recently characterized as an autosomal recessive disorder caused by an EHBP1L1 frameshift variant in English Springer Spaniels (ESSPs). The frequency and dissemination of the mutation remained unknown. The EHBP1L1 protein is essential for muscle function, and the Rab8/10-EHBP1L1-Bin1-dynamin axis participates in nuclear polarization during the enucleation of erythroblasts. Lack of EHBP1L1 function decreases enucleation, leading to increased numbers of nucleated erythrocytes, which are characteristic of DAMS. A genotyping survey for the EHBP1L1 variant was conducted based upon submitted samples of ESSPs from Europe. DNA was extracted, and a real-time PCR assay, with allele-specific TaqMan probes for EHBP1L1 wild-type and frameshift deletion, was applied. Between September 2022 and August 2024, 803 samples were received from 18 European countries. The EHBP1L1 mutant allele frequency was 9.7%, including 4 homozygous dogs and 148 heterozygotes. The mutant EHBP1L1 allele was found in 13 countries. A total of 6 homozygous and 73 heterozygous ESSPs reported on an open database could be tracked to an original common ancestor. Although the survey is biased, it indicates that the mutant EHBP1L1 variant is disseminated in the breed and across Europe. The genotyping of ESSPs is recommended to diagnose DAMS and guide breeders.

Alterations of the BRAF gene and the resulting changes in the BRAF protein are one example of molecular cancer profiling in humans and dogs. We tested 227 samples of canine carcinomas from different anatomical sites (anal sac (n = 23), intestine (n = 21), liver (n = 21), lungs (n = 19), mammary gland (n = 20), nasal cavity (n = 21), oral epithelium (n = 18), ovary (n = 20), prostate (n = 21), thyroid gland (n = 21), urinary bladder (n = 22)) with two commercially available primary anti-BRAFV600E antibodies (VE1 Ventana, VE1 Abcam). The immunohistochemical results were confirmed with droplet digital PCR (ddPCR). BRAFV595E-mutated cases were found in canine prostatic (16/21), urothelial (17/22), and oral squamous cell carcinomas (4/18), while other carcinoma types tested negative. Both antibodies showed consistent results, with intracytoplasmic immunolabeling of tumour cells, making them reliable tools for detecting the BRAFV595E mutation in canine carcinomas. In conclusion, identifying BRAF mutations from biopsy material offers a valuable opportunity to enhance cancer treatment strategies (BRAF inhibitors) in canine urothelial carcinomas, prostatic carcinomas, and oral squamous cell carcinomas.

This geoarchaeological survey was dedicated to (i) the Umm an-Nar (2700–2000 BCE) settlement site of Dahwa and surrounding areas in the foothills of the Hajar Mountains as well as (ii) the coastal area near Saham on the Batinah coastal plain in northern Oman, the latter without focus on a specific cultural epoch. Stratigraphic sections from the proximal coastal plain provide insights into highly dynamic episodic sedimentation patterns with thick units of variable grain sizes and sorting. In one of the stratigraphic profiles in the town of Saham, a small anthropogenic pit or channel was found, interpreted as a pit hearth used by the Samad culture (300 BCE–100/200 CE) based on granulometry, thin-section analysis, clustered macro-charcoals, amorphous organic remains, as well as luminescence and 14C dating. Our coincidental discovery of this site indicates that there might be abundant traces of the Samad culture buried in the thick alluvium, from a period of hydrologically favourable conditions c. 50–300 CE. The Umm an-Nar dating of the Dahwa archaeological site in the foothills of the Hajar Mountains was confirmed for the first time by luminescence dating, although the low dose rate and high scatter of equivalent doses pose substantial challenges to the regional application of this method.

Hantavirus pulmonary syndrome (HPS) is an American emerging disease caused by the rodent-borne virus genus Orthohantavirus (Family: Hantaviridae: Order: Elliovirales Class: Bunyaviricetes). In Argentina, almost half of the HPS infections occur in the northwestern endemic region. In this study, we monitored rodent abundance during 2022 and 2023 in three sites with different sampling methods (removal trapping, live trapping and hunted rodents by domestic cats) to evaluate their relationship with human infections. We found a similar pattern of variation in rodent abundance across time, and particularly a synchronous rise of rodent abundance that anticipated an HPS outbreak in 2023. Our dynamic regression models revealed a positive relationship between HPS cases and rodent abundance with a three-month lag, as well as rainfall with an eight-month lag. Our results provide a framework for the planning and implementation of public health prevention campaigns based on climatology and rodent monitoring. Domestic cats bringing rodents into houses can be an overlooked risk factor, particularly if viral shedding of infected rodents is magnified by stress. HPS is a disease of public health concern due to its high mortality rate, the lack of a specific therapeutic treatment and no vaccine. Thus, prevention of infections is of the utmost importance.

The potential of the arts and sciences for economic and social development is under conceptualized. However, the recent development of STEM (science, technology, engineering, and mathematics), justifying increased support for training in the sciences, shows a parallel pathway forward for the arts. The arts are increasingly relevant to the economy, amenable to policy influence as well as an area of human activity in their own right. The authors posit a unified arts framework: PAVAM (performing arts, visual arts, and music), complementing STEM as the basis for a strategy of arts-based interdisciplinary "industrial" policy making. The growing salience of the arts as an industrial sector in the UK and USA is shown. By identifying sources and pathways of value creation from the arts, clear entry points for policy action become identifiable to promote innovation, entrepreneurship, and economic development. Comparative case studies suggest a typology of the arts' potential as sources of creativity, innovation, and regional economic development.

Abstract Background Pediatric cardiac transplantation remains a surgical challenge as a variety of cardiac and vessel malformation are present in patients with congenital heart disease (CHD). Despite limited availability and acceptability of donor hearts, the number of heart transplantations remains on a stable level with improved survival and quality of life. Observation As treatment options for CHD continue to improve and the chances of survival increase, more adult CHD patients are listed for transplantation. This review focuses on the clinical challenges and modified techniques of pediatric heart transplantations. Conclusion Not only knowledge of the exact anatomy, but above all careful planning, interdisciplinary cooperation and surgical experience are prerequisites for surgical success.

Meltwater runoff from the Greenland ice sheet (GrIS) is an important contributor to global sea level rise, but substantial uncertainty exists in its measurement and prediction. Common approaches for estimating ice sheet runoff are in situ gauging of proglacial rivers draining the ice sheet and surface mass balance (SMB) modeling. To obtain hydrological and meteorological data sets suitable for both runoff stage characterization and, pending the establishment of stage–discharge curves, SMB model evaluation, we established an automated weather station (AWS) and a cluster of traditional and experimental river stage sensors on the Minturn River, the largest proglacial river draining Inglefield Land, NW Greenland. Secondary installations measuring river stage were installed in the Fox Canyon River and North River at Pituffik Space Base, NW Greenland. Proglacial runoff at these sites is dominated by supraglacial processes only, uniquely advantaging them for SMB studies. The three installations provide rare hydrological time series and an opportunity to evaluate experimental measurements of river stage from a harsh, little-studied polar region. The installed instruments include submerged vented and non-vented pressure transducers, a bubbler sensor, experimental bank-mounted laser rangefinders, and time-lapse cameras. The first 3 years of observations (2019 to 2021) from these stations indicate (a) a meltwater runoff season from late June to late August/early September that is roughly synchronous throughout the region; (b) the early onset (∼ 23 June to 8 July) of a strong diurnal runoff signal in 2019 and 2020, suggesting minimal meltwater storage in snow and/or firn; (c) 1 d lagged air temperature that displays the strongest correlation with river stage; (d) river stage that correlates more strongly with ablation zone albedo than with net radiation; and (e) the late-summer rain-on-ice events appear to trigger the region's sharpest and largest floods. The new gauging stations provide valuable in situ hydrological observations that are freely available through the PROMICE network (https://promice.org/weather-stations/, last access: 14 September 2023).

Abstract Background Longitudinal data on key cancer outcomes for clinical research, such as response to treatment and disease progression, are not captured in standard cancer registry reporting. Manual extraction of such outcomes from unstructured electronic health records is a slow, resource-intensive process. Natural language processing (NLP) methods can accelerate outcome annotation, but they require substantial labeled data. Transfer learning based on language modeling, particularly using the Transformer architecture, has achieved improvements in NLP performance. However, there has been no systematic evaluation of NLP model training strategies on the extraction of cancer outcomes from unstructured text. Results We evaluated the performance of nine NLP models at the two tasks of identifying cancer response and cancer progression within imaging reports at a single academic center among patients with non-small cell lung cancer. We trained the classification models under different conditions, including training sample size, classification architecture, and language model pre-training. The training involved a labeled dataset of 14,218 imaging reports for 1112 patients with lung cancer. A subset of models was based on a pre-trained language model, DFCI-ImagingBERT, created by further pre-training a BERT-based model using an unlabeled dataset of 662,579 reports from 27,483 patients with cancer from our center. A classifier based on our DFCI-ImagingBERT, trained on more than 200 patients, achieved the best results in most experiments; however, these results were marginally better than simpler “bag of words” or convolutional neural network models. Conclusion When developing AI models to extract outcomes from imaging reports for clinical cancer research, if computational resources are plentiful but labeled training data are limited, large language models can be used for zero- or few-shot learning to achieve reasonable performance. When computational resources are more limited but labeled training data are readily available, even simple machine learning architectures can achieve good performance for such tasks.

Wheat consumption represents a large part of human diet. The quality of wheat grains and derived products depends on the genotype and its interaction with the environment. This work aimed to identify the effects of different wheat genotypes grown in different environments, performing nutraceutical multitrait selection, seeking the wheat ideotype based on wheat quality indicators. In total, 16 wheat genotypes were evaluated in five environments, using two sowing times. The contents of proteins, lipids, fibers, mineral material, and carbohydrates were evaluated. The residual or restricted maximum likelihood/best linear unbiased prediction (REML/BLUP) methodology was used to estimate variance components and genetic parameters. Moreover, the multi-trait genotype-ideotype distance index (MGIDI) was used to select the genotypes that demonstrated superiority. Except for the lipid content, high values of genotypic variance were identified. FPS Certero, ORS 1403, LG Prisma, and Tbio Iguaçú genotypes, conducted in São Gabriel and Cachoeira do Sul, met the sought ideotype during the first sowing time. FPS Certero, Tbio Tibagi, and LG Supra genotypes were superior when conducted in the Santo Augusto environment during the second sowing time.

IntroductionNecrotizing meningoencephalitis (NME) in pugs is a potentially fatal disease, which needs lifelong treatment with immunosuppressive or immunomodulatory drugs and shares parallels with acute fulminating multiple sclerosis. Genetic variants of the DLA class II gene are associated with an increased risk for NME. Genetic testing is recommended prior to breeding. The aim of this study was to describe the current allele frequency of a previously identified NME risk variant in the European pug population. A secondary aim was to investigate the association of the NME risk variant with the clinical phenotype in pugs.MethodsResults of genetic testing for the CFA12:2605517delC variant in European pugs between 2012 and 2020 were retrieved (n = 5,974). A validated questionnaire was mailed to all submitters of samples for further information on neurological signs, diagnostic tests, and disease course.ResultsThe allele frequency of the CFA12 NME risk variant was 25.7% in the European pug population dogs; 7.4% of the dogs were homozygous and 36.7% were heterozygous for the NME risk variant on CFA12. Completed questionnaires were available in 203 dogs including 25 dogs with epileptic seizures or other neurological signs. The clinical phenotype was consistent with NME in 3.9% with a median age of onset of 1.0 years, and indicative of idiopathic epilepsy in 2.9% with a median onset of 2.5 years. Eleven dogs remained unclassified. Pugs with the NME phenotype were significantly more frequently homozygous for the NME risk variant on CFA12 compared to pugs ≥6 years without neurological signs or seizures (p = 0.008).DiscussionThe CFA12:2605517delC genetic risk variant is widely distributed in the European pug population and frequently homozygous in pugs with a NME phenotype. The data support the clinical relevance of the CFA12:2605517delC genetic risk variant.