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Background Chemokine CXC ligand 13 (CXCL13) has been implicated in perivascular inflammation and pulmonary vascular remodeling in patients with idiopathic pulmonary artery hypertension (IPAH). We wondered whether CXCL13 may also play a role in chronic thromboembolic pulmonary hypertension (CTEPH) and whether serum levels of CXCL13 might serve as biomarkers in these conditions. Methods Lung tissue from patients with IPAH or CTEPH was immunostained for CXCL13. Serum samples were obtained from patients with IPAH ( n  = 42) or CTEPH ( n  = 50) and from healthy controls ( n  = 13). Serum CXCL13 concentrations were measured by enzyme-linked immunosorbent assay technology and were evaluated for associations with markers of disease severity and survival. Results CXCL13 was expressed in pulmonary vascular lesions and lymphocytes of patients with IPAH and inoperable CTEPH, respectively. Serum CXCL13 was elevated in patients compared to healthy controls [median, interquartile range, 83 (55,114) pg/ml versus 40 (28, 48) pg/ml; p  < 0.001]. Serum CXCL13 showed only weak and inconsistent correlations with markers of inflammation or disease severity. In both populations, patients with serum CXCL13 above the median of the respective groups did not have a higher risk of death than patients with lower serum CXCL13. Conclusions CXCL13 was overexpressed in pulmonary vascular lesions of patients with IPAH and CTEPH, and increased serum concentrations were found in patients with IPAH and CTEPH, suggesting a potential pathogenic role of CXCL13 in both diseases. However, given the weak associations between serum CXCL13 and markers of disease severity and outcome, CXCL13 is unlikely to become a promising biomarker in these patient populations.

An essential aspect of male reproductive capacity is the immediate availability of fertilization‐ready spermatozoa. To ensure this, most mammals rely on post‐testicular sperm maturation. In epididymis, germ cells are matured and stored in a quiescent state that readily can be altered to produce active spermatozoa. This depends on active proton secretion into the epididymal lumen. We have identified Foxi1 as an important regulator of gene expression in narrow and clear cells—the major proton secretory cells of epididymal epithelia. Foxi1 appears to be required for the expression of the B1‐subunit of the vacuolar H + ‐ATPase proton pump and for carbonic anhydrase II as well as the chloride/bicarbonate transporter pendrin. Using transfection experiments, we have identified a Foxi1 binding cis ‐element in the ATP6V1B1 (encoding the B1‐subunit) promoter that is critical for reporter gene activation. When this site is mutated to eliminate Foxi1 binding, activation is also abolished. As a consequence of defect Foxi1‐dependent epididymal sperm maturation, we demonstrate that spermatozoa from Foxi1 null males fail to reach the female genital tract in sufficient number to allow fertilization.

Background: Data on the incidence and comorbidity of Lichen sclerosus (LS), based on validated nationwide population-based registries, remains scarce. Objective: To explore the incidence and association of comorbidities with LS in Sweden, emphasizing its potential links to malignancies and autoimmune disorders. Methods: A population-based retrospective open cohort study was conducted using the National Patient Register to identify all individuals diagnosed with LS (ICD-10 code L90.0) from 1 January 2001 to 1 January 2021. The study included 154,424 LS patients and a sex and age matched control group of 463,273 individuals to assess the incidence and odds ratios for various cancers and premalignant conditions. Results: The incidence of LS in Sweden was 80.9 per 100,000 person per year, with higher incidence in females (114.4) than in males (47.2). LS patients showed an increased odds ratio for vulvar cancer (OR = 8.3; 95% CI = 7.5–9.0), penile cancer (OR = 8.9; 95% CI = 7.3–11.0), prostate cancer (OR = 1.2; 95% CI = 1.1–1.2), testicular cancer (OR = 1.4; 95% CI = 1.1–1.7), bladder cancer (OR = 1.1; 95% CI = 1.1–1.2), breast cancer (OR = 1.4; 95% CI = 1.3–1.4), leukoplakia of the vulva (OR = 253.5; 95% CI = 221.9–289.6), and leukoplakia of the penis (OR = 5.1; 95% CI = 4.9–5.4). Conclusions: This study underscores the significantly increased association of various cancers and premalignant conditions in LS patients, highlighting the critical need for efficacious treatment and diligent follow-up. The association between LS and autoimmune diseases further necessitates comprehensive investigation to understand the underlying mechanisms and clinical management implications. Future research is essential to confirm these findings and elucidate the role of LS in cancer development.

Recent findings suggest that nuclear IGF1R binds to enhancer regions and functions as a transcriptional cofactor. However, the downstream transcriptional regulators of this pathway remain to be defined. Here, we show that nuclear IGF1R associates with the transcription factor LEF1 and increases promoter activity of LEF1 downstream target genes cyclin D1 and axin2 . Furthermore, nuclear IGF1R augments protein levels of cyclin D1 and axin2. Our findings suggest a novel function for IGF1R, thus further emphasizing the important role of this receptor in cancer biology. Insulin growth factor 1 receptor is known to translocate to the nucleus upon IGF1 signalling. Sehat and collaborators show in this report that nuclear IGFR1 is a transcriptional co‐factor of LEF1/TCF required for cyclin D and axin2 activation independently of β‐catenin.

Birds have excellent spatial acuity and colour vision compared to other vertebrates while spatial contrast sensitivity is relatively poor for unknown reasons. Contrast sensitivity describes the detection of gratings of varying spatial frequency. It is unclear whether bird brightness discrimination between large uniform fields is poor as well. Here we show that budgerigars (Melopsittacus undulatus) need a Michelson contrast of 0.09 to discriminate between large spatially separated achromatic fields in bright light conditions. This is similar to the peak contrast sensitivity of 10.2 (0.098 Michelson contrast) for achromatic grating stimuli established in earlier studies. The brightness discrimination threshold described in Weber fractions is 0.18, which is modest compared to other vertebrates.

Tumors of soft tissue and bone represent a heterogeneous group of neoplasias characterized by a wide variety of genetic aberrations. Albeit knowledge on tumorigenesis in mesenchymal tumors is continuously increasing, specific insights on altered signaling pathways as a basis for molecularly targeted therapeutic strategies are still sparse. The aim of this study was to determine the involvement of YAP1/TAZ-mediated signals in tumors of soft tissue and bone. Expression levels of YAP1 and TAZ were analyzed by immunohistochemistry in a large cohort of 486 tumor specimens, comprising angiosarcomas (AS), Ewing sarcomas, leiomyosarcomas, malignant peripheral nerve sheath tumors (MPNST), solitary fibrous tumors, synovial sarcomas (SySa), well-differentiated/dedifferentiated/pleomorphic and myxoid liposarcomas (MLS). Moderate to strong nuclear staining of YAP1 and TAZ was detected in 53% and 33%, respectively. YAP1 nuclear expression was most prevalent in MPNST, SySa and MLS, whereas nuclear TAZ was predominately detected in AS, MLS and MPNST. In a set of sarcoma cell lines, immunoblotting confirmed nuclear localization of YAP1 and TAZ, corresponding to their transcriptionally active pool. Suppression of YAP1/TAZ-TEAD mediated transcriptional activity significantly impaired sarcoma cell viability in vitro and in vivo . Our findings identify nuclear YAP1 and TAZ positivity as a common feature in subsets of sarcomas of soft tissue and bone and provide evidence of YAP1/TAZ-TEAD signaling as a specific liability to be considered as a new target for therapeutic intervention. Nuclear YAP1/TAZ expression may represent a biomarker suited to identify patients that could benefit from YAP1/TAZ-TEAD directed therapeutic approaches within future clinical trials.

Limited knowledge exists about ∼100-m-scale precipitation processes within U.S. northeast coastal snowstorms because of a lack of high-resolution observations. We investigate characteristics of microscale updraft regions within the cyclone comma head and their relationships with snowbands, wind shear, frontogenesis, and vertical mass flux using high-spatiotemporal-resolution vertically pointing Ka-band radar measurements, soundings, and reanalysis data for four snowstorms observed at Stony Brook, New York. Updraft regions are defined as contiguous time–height plotted areas with upward Doppler velocity without hydrometeor sedimentation that is equal to or greater than 0.4 m s −1 . Most updraft regions in the time–height data occur on a time scale of seconds (<20 s), which is equivalent to spatial scales < 500 m. These small updraft regions within cloud echo occur more than 30% of the time for three of the four cases and 18% for the other case. They are found at all altitudes and can occur with or without frontogenesis and with or without snowbands. The updraft regions with relatively large Doppler spectrum width (>0.4 m s −1 ) occur more frequently within midlevels of the storms, where there are strong wind shear layers and moist shear instability layers. This suggests that the dominant forcing for the updrafts appears to be turbulence associated with the vertical shear instability. The updraft regions can be responsible for upward mass flux when they are closer together in space and time. The higher values of column mean upward mass flux often occur during snowband periods.

For a bird, it is often vital to visually detect food items, predators, or individuals from the same flock, i.e. moving stimuli of various shapes. Yet, behavioural tests of visual spatial acuity traditionally use stationary gratings as stimuli. We have behaviourally tested the ability of budgerigars (Melopsittacus undulatus) to detect a black circular target, moving semi-randomly at 1.69 degrees s−1 against a brighter background. We found a detection threshold of 0.107±0.007 degrees of the visual field for a target size corresponding to a resolution of a grating with a spatial frequency of 4.68 cycles degree−1. This detection threshold is lower than the resolution limit for gratings but similar to the threshold for stationary single objects of the same shape. We conclude that the target acuity of budgerigars for moving single targets, just as for stationary single targets, is lower than their acuity for gratings.

Bismuth-based compounds, such as Bi1 -x Sb x or Bi 2 Te 3 , have outstanding electronic properties especially for advanced quantum devices. However, the potential of low-dimensional group V-Bi materials is largely undetermined. Here, we report the experimental realization of a two-dimensional (2D) BiAs layer with giant Rashba spin splitting, grown on an InAs(111)B substrate via molecular beam epitaxy. ARPES reveals the emergence of a prominent M-shaped band structure and a distinct electron pocket at the Fermi level. DFT, complemented by synchrotron-based XPS, LEED, and STM, confirms strong spin-orbit coupling and a giant Rashba coefficient of these electronic states. An As overlayer, remaining from the fabrication process, preserves a structural shift between substrate and BiAs layer, essential for the Rashba splitting, while preventing undesirable reconstruction. This indicates how well-known capping techniques can stabilize new 2D compounds with interesting electronic structures, especially BiAs, a promising candidate to open possibilities for next-generation spintronic devices and field-effect transistors. Bismuth-based compounds are known for their exceptional electronic properties, yet the potential of low-dimensional group V-Bi materials remains largely unexplored. Here, the authors experimentally realize a 2D BiAs layer with giant Rashba spin splitting, revealing its potential for next-generation spintronic devices and field-effect transistors through advanced characterization techniques.

Protected area (PA) is an indicator linked to policies on ecological sustainability. We analyzed area, size, and categories of PAs in the European boreal forest biome in Norway, Sweden, Finland, and Russia from 1900 to 2010. The PA increased from 1.5 × 103 ha in 1909 to 2.3 × 107 ha in 2010. While the total PA in the boreal biome was 10.8 %, the figures ranged from 17.2 % in the northern, 7.9 % of the middle, and 8.7 % of the southern boreal sub-regions. The median size of PAs varied from 10 to 124 ha among countries. The categories of less strictly PAs increased over time. The proportion of area occupied by PAs is an important response indicator for conservation efforts. However, the use of PA as an indicator of ecological sustainability needs to consider ecosystem representation, functional connectivity and management categories.