Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window

During the implantation window, the endometrium becomes poised to transition to a pregnant state, a process driven by differentiation of stromal cells into decidual cells (DC). Perturbations in this process, termed decidualization, leads to breakdown of the feto-maternal interface and miscarriage, but the underlying mechanisms are poorly understood. Here, we reconstructed the decidual pathway at single-cell level in vitro and demonstrate that stromal cells first mount an acute stress response before emerging as DC or senescent DC (snDC). In the absence of immune cell-mediated clearance of snDC, secondary senescence transforms DC into progesterone-resistant cells that abundantly express extracellular matrix remodelling factors. Additional single-cell analysis of midluteal endometrium identified DIO2 and SCARA5 as marker genes of a diverging decidual response in vivo. Finally, we report a conspicuous link between a pro-senescent decidual response in peri-implantation endometrium and recurrent pregnancy loss, suggesting that pre-pregnancy screening and intervention may reduce the burden of miscarriage

EndoTime: non-categorical timing estimates for luteal endometrium

STUDY QUESTION Can the accuracy of timing of luteal phase endometrial biopsies based on urinary ovulation testing be improved by measuring the expression of a small number of genes and a continuous, non-categorical modelling approach? SUMMARY ANSWER Measuring the expression levels of six genes (IL2RB, IGFBP1, CXCL14, DPP4, GPX3 and SLC15A2) is sufficient to obtain substantially more accurate timing estimates and to assess the reliability of timing estimates for each sample. WHAT IS KNOWN ALREADY Commercially available endometrial timing approaches based on gene expression require large gene sets and use a categorical approach that classifies samples as pre-receptive, receptive or post-receptive. STUDY DESIGN, SIZE, DURATION Gene expression was measured by RTq-PCR in different sample sets, comprising a total of 664 endometrial biopsies obtained 4–12 days after a self-reported positive home ovulation test. A further 36 endometrial samples were profiled by RTq-PCR as well as RNA-sequencing. PARTICIPANTS/MATERIALS, SETTING, METHODS A computational procedure, named ‘EndoTime’, was established that models the temporal profile of each gene and estimates the timing of each sample. Iterating these steps, temporal profiles are gradually refined as sample timings are being updated, and confidence in timing estimates is increased. After convergence, the method reports updated timing estimates for each sample while preserving the overall distribution of time points. MAIN RESULTS AND THE ROLE OF CHANCE The Wilcoxon rank-sum test was used to confirm that ordering samples by EndoTime estimates yields sharper temporal expression profiles for held-out genes (not used when determining sample timings) than ordering the same expression values by patient-reported times (GPX3: P  0.05). LARGE SCALE DATA The RTq-PCR data files are available via the GitHub repository for the EndoTime software at https://github.com/AE-Mitchell/EndoTime, as is the code used for pre-processing of RTq-PCR data. The RNA-sequencing data are available on GEO (accession GSE180485). LIMITATIONS, REASONS FOR CAUTION Timing estimates are informed by glandular gene expression and will only represent the temporal state of other endometrial cell types if in synchrony with the epithelium. Methods that estimate the day of ovulation are still required as these data are essential inputs in our method. Our approach, in its current iteration, performs batch correction such that larger sample batches impart greater accuracy to timing estimations. In theory, our method requires endometrial samples obtained at different days in the luteal phase. In practice, however, this is not a concern as timings based on urinary ovulation testing are associated with a sufficient level of noise to ensure that a variety of time points will be sampled. WIDER IMPLICATIONS OF THE FINDINGS Our method is the first to assay the temporal state of luteal-phase endometrial samples on a continuous domain. It is freely available with fully shared data and open-source software. EndoTime enables accurate temporal profiling of any gene in luteal endometrial samples for a wide range of research applications and, potentially, clinical use

Genetic turnovers and northern survival during the last glacial maximum in European brown bears.

The current phylogeographic pattern of European brown bears (Ursus arctos) has commonly been explained by postglacial recolonization out of geographically distinct refugia in southern Europe, a pattern well in accordance with the expansion/contraction model. Studies of ancient DNA from brown bear remains have questioned this pattern, but have failed to explain the glacial distribution of mitochondrial brown bear clades and their subsequent expansion across the European continent. We here present 136 new mitochondrial sequences generated from 346 remains from Europe, ranging in age between the Late Pleistocene and historical times. The genetic data show a high Late Pleistocene diversity across the continent and challenge the strict confinement of bears to traditional southern refugia during the last glacial maximum (LGM). The mitochondrial data further suggest a genetic turnover just before this time, as well as a steep demographic decline starting in the mid-Holocene. Levels of stable nitrogen isotopes from the remains confirm a previously proposed shift toward increasing herbivory around the LGM in Europe. Overall, these results suggest that in addition to climate, anthropogenic impact and inter-specific competition may have had more important effects on the brown bear's ecology, demography, and genetic structure than previously thought

Winter Temperature and Forest Cover Have Shaped Red Deer Distribution in Europe and the Ural Mountains Since the Late Pleistocene

Aim: The Expansion-Contraction model has been used to explain the responses of species to climatic changes. During periods of unfavourable climatic conditions, species retreat to refugia from where they may later expand. This paper focuses on the palaeoecology of red deer over the past 54 ka across Europe and the Urals, to reveal patterns of change in their range and explore the role of environmental conditions in determining their distribution. Location: Europe and western Asia to 63°E. Taxon: Red deer (Cervus elaphus). Methods: We collected 984 records of radiocarbon-dated red deer subfossils from the Late Pleistocene and the Holocene, including 93 original dates. For each deer sample we compiled climatic and biome type data for the corresponding time intervals. Results: During the last 54 ka changes in red deer range in Europe and the Urals were asynchronous and differed between western and eastern Europe and western Asia due to different environmental conditions in those regions. The range of suitable areas for deer during the Last Glacial Maximum (LGM) was larger than previously thought and covered vast regions not only in southern but also in western and eastern Europe. Throughout the period investigated the majority of specimens inhabited forests in the temperate climatic zone. The contribution of forests in deer localities significantly decreased during the last 4 ka, due to deforestation of Europe caused by humans. Mean January temperature was the main limiting factor for species distribution. Over 90% of the samples were found in areas where mean January temperature was above −10°C. Main conclusions: Red deer response to climatic oscillations are in agreement with the Expansion-Contraction model but in contradiction to the statement of only the southernmost LGM refugia of the species. During the last 54 ka red deer occurred mostly in forests of the temperate climatic zone. © 2020 John Wiley & Sons Ltd.European Social Fund, Grant/Award Number: UDA-POKL.04.01.01-00-072/09-00; University of Wroclaw, Grant/Award Number: 0410/2990/18; Institute of Environmental Biology, University of Wrocław, Grant/Award Number: 0410/2990/18; Mammal Research Institute Polish Academy of Sciences; Narodowe Centrum Nauki , Grant/Award Number: DEC-2013/11/B/NZ8/00888 and UMO-2016/23/B/HS3/00387; Romanian National Authority for Scientific Research, UEFISCDI, Grant/Award Number: PN-IIIP4-ID-PCE-2016-0676; National Centre for Atmospheric Science and the Centre for Environmental Data Analysis, UK; Faunal Database of the Stage Three Project; Leverhulme Trust, Grant/Award Number: F00568W

Winter temperature and forest cover have shaped red deer distribution in Europe and the Ural Mountains since the Late Pleistocene

Aim: The Expansion-Contraction model has been used to explain the responses of species to climatic changes. During periods of unfavourable climatic conditions, species retreat to refugia from where they may later expand. This paper focuses on the palaeoecology of red deer over the past 54 ka across Europe and the Urals, to reveal patterns of change in their range and explore the role of environmental conditions in determining their distribution. Location: Europe and western Asia to 63°E. Taxon: Red deer (Cervus elaphus). Methods: We collected 984 records of radiocarbon-dated red deer subfossils from the Late Pleistocene and the Holocene, including 93 original dates. For each deer sample we compiled climatic and biome type data for the corresponding time intervals. Results: During the last 54 ka changes in red deer range in Europe and the Urals were asynchronous and differed between western and eastern Europe and western Asia due to different environmental conditions in those regions. The range of suitable areas for deer during the Last Glacial Maximum (LGM) was larger than previously thought and covered vast regions not only in southern but also in western and eastern Europe. Throughout the period investigated the majority of specimens inhabited forests in the temperate climatic zone. The contribution of forests in deer localities significantly decreased during the last 4 ka, due to deforestation of Europe caused by humans. Mean January temperature was the main limiting factor for species distribution. Over 90% of the samples were found in areas where mean January temperature was above −10°C. Main conclusions: Red deer response to climatic oscillations are in agreement with the Expansion-Contraction model but in contradiction to the statement of only the southernmost LGM refugia of the species. During the last 54 ka red deer occurred mostly in forests of the temperate climatic zone. © 2020 John Wiley & Sons Ltd.European Social Fund, Grant/Award Number: UDA-POKL.04.01.01-00-072/09-00; University of Wroclaw, Grant/Award Number: 0410/2990/18; Institute of Environmental Biology, University of Wrocław, Grant/Award Number: 0410/2990/18; Mammal Research Institute Polish Academy of Sciences; Narodowe Centrum Nauki , Grant/Award Number: DEC-2013/11/B/NZ8/00888 and UMO-2016/23/B/HS3/00387; Romanian National Authority for Scientific Research, UEFISCDI, Grant/Award Number: PN-IIIP4-ID-PCE-2016-0676; National Centre for Atmospheric Science and the Centre for Environmental Data Analysis, UK; Faunal Database of the Stage Three Project; Leverhulme Trust, Grant/Award Number: F00568W

Wpływ odmiany na wzrost i zależności między cechami wzrostu drzew jabłoni typu „knip-boom”

The measurements have been performed in the nursery in the years 2007–2013 to study differences in size and correlations between selected growth factors in “knipboom” trees of 6 apple cultivars on M.9 rootstock. The trees of ‘Jonagold Decosta’ (‘Red Jonaprince’ in 2013) and ‘Fuji Beni Shogun’ showed the strongest growth, ‘Šampion’ and ‘Camspur’ the weakest one, whereas ‘Gala Must’ and ‘Golden Delicious Reinders’ were characterized by moderate vigor. Mean length of one feather increased from the tree top towards its base, but did not depend significantly on the number of laterals per tree. Correlations between growth factors were similar to those found in maiden apple trees and the closest ones were between total length of lateral shoots and their number on the tree. A trunk diameter had stronger correlations with other growth parameters than tree height.Pomiarów dokonano w szkółce w latach 2007–2013 w celu zbadania różnic we wzroście i określenia korelacji pomiędzy wybranymi cechami wzrostowymi drzewek typu „knip boom” sześciu odmian jabłoni na podkładce M.9. Najsilniejszy wzrost wykazywały drzewka ‘Jonagold Decosta’ (‘Red Jonaprince’ w 2013) i ‘Fuji Beni Shogun’, natomiast najsłabszy ‘Šampion’ i ‘Camspur’, podczas gdy ‘Gala Must’ i ‘Golden Delicious Reinders’ charakteryzowały się średnią siłą wzrostu. Średnia długość pędu bocznego zwiększała się od szczytu drzewka do jego podstawy, lecz nie była istotnie zależna od liczby pędów bocznych. Korelacje pomiędzy cechami wzrostu były podobne do, tych jakie zaobserwowano w przypadku okulantów, przy czym najsilniejsza była zależność pomiędzy całkowitą długością pędów bocznych i ich liczbą na drzewie. Średnica pnia była silniej skorelowana z innymi cechami wzrostowymi, niż wysokość drzewek

Wind action on steel chimneys according to standards

W artykule przedstawiono analizę odpowiedzi kominów stalowych na oddziaływanie wiatru. Rozpatrzono podejścia zastosowane w normach polskich: dotyczącej kominów stalowych [1] i wiatrowej [2] oraz w Eurokodzie 1 [3]. Porównano oddziaływania w linii wiatru według poszczególnych procedur, a także w kierunku prostopadłym do średniej prędkości wiatru, które jest wywołane wzbudzeniem wirowym oraz odpowiedzi kominów na te obciążenia wyrażone za pomocą przemieszczeń wierzchołków. Do analiz przyjęto istniejące kominy stalowe, które niemal wszystkie uległy awariom, głównie wskutek wzbudzenia wirowego. Wszystkie kominy i oddziaływania zostały zamodelowane w programie MES – Autodesk Mechanical Simulation 2013.Analysis of the steel chimneys response to the wind action has been presented in the paper. The approaches presented in the Polish standards: referring to the steel chimneys [1] and to the wind action [2], as well as in the Eurocode 1 [3] have been shown here. The comparisons of the inline wind action according to these procedures, as well as in the cross-wind directions have been made. The responses to the wind action, i.e. displacements at the top of each chimney, have been compared as well. The real chimneys have been subjected to the analyses. Almost each of them had collapsed, mainly because of the vortex excitation. All chimneys and wind actions have been modelled by FEM system – Autodesk Mechanical Simulation 2013