Nuclear Pores Promote Lethal Prostate Cancer by Increasing POM121-Driven E2F1, MYC, and AR Nuclear Import.

Nuclear pore complexes (NPCs) regulate nuclear-cytoplasmic transport, transcription, and genome integrity in eukaryotic cells. However, their functional roles in cancer remain poorly understood. We interrogated the evolutionary transcriptomic landscape of NPC components, nucleoporins (Nups), from primary to advanced metastatic human prostate cancer (PC). Focused loss-of-function genetic screen of top-upregulated Nups in aggressive PC models identified POM121 as a key contributor to PC aggressiveness. Mechanistically, POM121 promoted PC progression by enhancing importin-dependent nuclear transport of key oncogenic (E2F1, MYC) and PC-specific (AR-GATA2) transcription factors, uncovering a pharmacologically targetable axis that, when inhibited, decreased tumor growth, restored standard therapy efficacy, and improved survival in patient-derived pre-clinical models. Our studies molecularly establish a role of NPCs in PC progression and give a rationale for NPC-regulated nuclear import targeting as a therapeutic strategy for lethal PC. These findings may have implications for understanding how NPC deregulation contributes to the pathogenesis of other tumor types.

Analysis of pea mutants reveals the conserved role of FRUITFULL controlling the end of flowering and its potential to boost yield.

Monocarpic plants have a single reproductive phase in their life. Therefore, flower and fruit production are restricted to the length of this period. This reproductive strategy involves the regulation of flowering cessation by a coordinated arrest of the growth of the inflorescence meristems, optimizing resource allocation to ensure seed filling. Flowering cessation appears to be a regulated phenomenon in all monocarpic plants. Early studies in several species identified seed production as a major factor triggering inflorescence proliferative arrest. Recently, genetic factors controlling inflorescence arrest, in parallel to the putative signals elicited by seed production, have started to be uncovered in Arabidopsis, with the MADS-box gene FRUITFULL (FUL) playing a central role in the process. However, whether the genetic network regulating arrest is also at play in other species is completely unknown. Here, we show that this role of FUL is not restricted to Arabidopsis but is conserved in another monocarpic species with a different inflorescence structure, field pea, strongly suggesting that the network controlling the end of flowering is common to other plants. Moreover, field trials with lines carrying mutations in pea FUL genes show that they could be used to boost crop yield.

Transcription factors HB21/40/53 trigger inflorescence arrest through abscisic acid accumulation at the end of flowering.

Flowers, and hence, fruits and seeds, are produced by the activity of the inflorescence meristem after the floral transition. In plants with indeterminate inflorescences the final number of flowers produced by the inflorescence meristem is determined by the length of the flowering period, which ends with inflorescence arrest. Inflorescence arrest depends on many different factors, such as the presence of seeds, the influence of the environment, or endogenous factors such as phytohormone levels and age, which modulate inflorescence meristem activity. The FRUITFULL-APETALA2 (FUL-AP2) pathway plays a major role in regulating the end of flowering, likely integrating both endogenous cues and those related to seed formation. Among AP2 targets, HOMEOBOX PROTEIN21 (HB21) has been identified as a putative mediator of AP2 function in the control of inflorescence arrest. HB21 is a homeodomain leucine zipper transcription factor involved in establishing axillary bud dormancy. Here we characterized the role of HB21 in the control of the inflorescence arrest at the end of flowering in Arabidopsis (Arabidopsis thaliana). HB21, together with HB40 and HB53, are upregulated in the inflorescence apex at the end of flowering, promoting floral bud arrest. We also show that abscisic acid (ABA) accumulation occurs in the inflorescence apex in an HB-dependent manner. Our work suggests a physiological role of ABA in floral bud arrest at the end of flowering, pointing to ABA as a regulator of inflorescence arrest downstream of the HB21/40/53 genes.

Latent trajectories of recent and delayed memory and their predictors: evidence from SHARE.

OBJECTIVES: Cognitive decline is common in the old age, but some evidence suggests it may already occur during adulthood. Previous studies have linked age, gender, educational attainment, depression, physical activity, and social engagement to better cognitive performance over time. However, most studies have used global measures of cognition, which could mask subtle changes in specific cognitive domains. The aim of this study is to examine trajectories of recent and delayed memory recall from a variable-centered perspective, in order to elucidate the impact of age, gender, educational attainment, depression, physical activity, and social engagement on recent and delayed memory both at initial time and across a 10-year period. DESIGN AND PARTICIPANTS: The sample was formed by 56,616 adults and older adults that participated in waves 4 to 8 of the Survey of Health, Aging and Retirement in Europe (SHARE). ANALYSES: We used latent growth modeling to establish latent recent and delayed memory trajectories, and then tested the effects of the aforementioned covariates on the latent intercept and slopes. RESULTS: Results showed that both recent and delayed recall display a quadratic trajectory of decline. All covariates significantly explained initial levels of immediate and delayed recall, but only a few had statistically significant effects on the slope terms. CONCLUSIONS: We discuss differences between present results and those previously reported in studies using a person-centered approach. This study provides evidence of memory decline during adulthood and old adulthood. Further, results provide support for the neural compensation reserve theory.

Social participation, loneliness, and physical inactivity over time: evidence from SHARE.

OBJECTIVES: We aimed to explore the reciprocal effects of social participation, loneliness, and physical inactivity over a period of 6 years in a representative sample of European adults over 50 years old. DESIGN: A longitudinal study with a six-year follow-up period was conducted. SETTING: Four waves of the Survey of Health, Ageing and Retirement in Europe project were used. PARTICIPANTS: This study includes 64,887 participants from Europe and Israel, who were aged 50 or older at the first time. MEASUREMENTS: The relationship between participation in social activities, loneliness and physical inactivity was analyzed, controlling for age, gender, and disability. A series of cross-lagged panel models (CLPMs) were applied to analyze the relationships among these variables. RESULTS: A CLPM with equal autoregressive cross-lagged effects across waves was the best fit to the data (χ2 = 7137.8, CFI = .972, RMSEA = .049, SRMR = .036). The autoregressive effects for the three variables showed high stability across waves, and all the cross-lagged effects in the model were statistically significant. Social activity and physical inactivity maintained a strong negative cross-lagged effect, while their cross-lagged effects on loneliness were comparatively smaller. Social activity had a positive cross-lagged effect on loneliness, while physical inactivity had a negative cross-lagged effect on loneliness. CONCLUSIONS: These findings highlight the importance of promoting physical activity and social participation and addressing loneliness through targeted interventions in older adults.

Impaired Mineral Ion Metabolism in a Mouse Model of Targeted Calcium-Sensing Receptor (CaSR) Deletion from Vascular Smooth Muscle Cells.

BACKGROUND: Impaired mineral ion metabolism is a hallmark of CKD-metabolic bone disorder. It can lead to pathologic vascular calcification and is associated with an increased risk of cardiovascular mortality. Loss of calcium-sensing receptor (CaSR) expression in vascular smooth muscle cells exacerbates vascular calcification in vitro. Conversely, vascular calcification can be reduced by calcimimetics, which function as allosteric activators of CaSR. METHODS: To determine the role of the CaSR in vascular calcification, we characterized mice with targeted Casr gene knockout in vascular smooth muscle cells ( SM22α CaSR Δflox/Δflox ). RESULTS: Vascular smooth muscle cells cultured from the knockout (KO) mice calcified more readily than those from control (wild-type) mice in vitro. However, mice did not show ectopic calcifications in vivo but they did display a profound mineral ion imbalance. Specifically, KO mice exhibited hypercalcemia, hypercalciuria, hyperphosphaturia, and osteopenia, with elevated circulating fibroblast growth factor 23 (FGF23), calcitriol (1,25-D3), and parathyroid hormone levels. Renal tubular α-Klotho protein expression was increased in KO mice but vascular α-Klotho protein expression was not. Altered CaSR expression in the kidney or the parathyroid glands could not account for the observed phenotype of the KO mice. CONCLUSIONS: These results suggest that, in addition to CaSR's established role in the parathyroid-kidney-bone axis, expression of CaSR in vascular smooth muscle cells directly contributes to total body mineral ion homeostasis.

[Influence of the COVID-19 pandemic on the epidemiology of acute bronchiolitis]. / Influencia de la pandemia COVID-19 sobre la epidemiología de la bronquiolitis aguda.

Introduction: The COVID-19 pandemic has changed the circulation of some viruses associated with acute bronchiolitis. We analyzed the epidemiology of bronchiolitis admissions during the COVID-19 pandemic compared with 8 previous epidemic seasons. Methods: An observational and ambispective study was performed, including infants admitted with bronchiolitis in a tertiary hospital during 2 periods: COVID-19 pandemic (15th March 2020 to 3 rd August 2021) and pre-pandemic (1st September 2012 to 14th March 2020). Demographic, clinical data and etiologies were collected. Results: Five hundred ten patients were hospitalized with bronchiolitis: 486 in the pre-pandemic period with an average of 61 admissions per season vs. 24 during the pandemic, observing a 60.7% reduction in bronchiolitis admissions. During the pandemic, bronchiolitis outbreak was delayed until spring-summer 2021. Respiratory syncytial virus was the most frequent etiological agent in both periods. Conclusion: We observed a change in the seasonality of bronchiolitis during the pandemic COVID-19, possibly influenced by control measures against SARS-CoV-2.

High SARS-CoV-2 Viral Load and Low CCL5 Expression Levels in the Upper Respiratory Tract Are Associated With COVID-19 Severity.

Mucosal immune response in the upper respiratory tract is crucial for initial control of viral replication, clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and progression of coronavirus disease 2019 (COVID-19). We analyzed SARS-CoV-2 RNA load and expression of selected immune genes in the upper respiratory tract (nasopharynx) of 255 SARS-CoV-2-infected patients and evaluated their association with severe COVID-19. SARS-CoV-2 replication in nasopharyngeal mucosa induces expression of several innate immune genes. High SARS-CoV-2 viral load and low CCL5 expression levels were associated with intensive care unit admission or death, although CCL5 was the best predictor of COVID-19 severity.

A cryptic variation in a member of the Ovate Family Proteins is underlying the melon fruit shape QTL fsqs8.1.

KEY MESSAGE: The gene underlying the melon fruit shape QTL fsqs8.1 is a member of the Ovate Family Proteins. Variation in fruit morphology is caused by changes in gene expression likely due to a cryptic structural variation in this locus. Melon cultivars have a wide range of fruit morphologies. Quantitative trait loci (QTL) have been identified underlying such diversity. This research focuses on the fruit shape QTL fsqs8.1, previously detected in a cross between the accession PI 124112 (CALC, producing elongated fruit) and the cultivar 'Piel de Sapo' (PS, producing oval fruit). The CALC fsqs8.1 allele induced round fruit shape, being responsible for the transgressive segregation for this trait observed in that population. In fact, the introgression line CALC8-1, carrying the fsqs8.1 locus from CALC into the PS genetic background, produced perfect round fruit. Following a map-based cloning approach, we found that the gene underlying fsqs8.1 is a member of the Ovate Family Proteins (OFP), CmOFP13, likely a homologue of AtOFP1 and SlOFP20 from Arabidopsis thaliana and tomato, respectively. The induction of the round shape was due to the higher expression of the CALC allele at the early ovary development stage. The fsqs8.1 locus showed an important structural variation, being CmOFP13 surrounded by two deletions in the CALC genome. The deletions are present at very low frequency in melon germplasm. Deletions and single nucleotide polymorphisms in the fsqs8.1 locus could not be not associated with variation in fruit shape among different melon accessions, what indicates that other genetic factors should be involved to induce the CALC fsqs8.1 allele effects. Therefore, fsqs8.1 is an example of a cryptic variation that alters gene expression, likely due to structural variation, resulting in phenotypic changes in melon fruit morphology.

Phased Array Antenna Analysis Workflow Applied to Gateways for LEO Satellite Communications.

Nowadays, mega-constellations of Low Earth Orbit (LEO) satellites have become increasingly important to provide high-performance Internet access with global coverage. This paper provides an updated comparison of four of the largest LEO mega-constellations: Telesat, SpaceX, OneWeb and Amazon. It describes the gateway design workflow from the patch antenna to phased array analysis. Patch antennas are developed for both transmission and reception after a thorough examination of the four systems. The results of electromagnetic simulation using Advanced Design Software (ADS) Momentum are shown, including their radiation pattern. Finally, a model of the gateway phased array using SystemVue is obtained using hexagonal, circular, and square arrays. According to the required effective isotropic radiated power (EIRP) and gain, the antenna sizes for the four constellations are estimated. As an example, for SpaceX constellation, a reception antenna with 8910 radiating elements using a hexagonal distribution with a gain of 46.9 dB and a sensitivity of -113.1 dBm was obtained.

A Cross-Sectional Study Examining the Association between Physical Activity and Perinatal Depression.

Background and Objectives: International organisations recommend that women without illness should have regular moderate-intensity physical exercise throughout their pregnancy and postpartum period as a measure to prevent possible pathologies in both the mother and the newborn. Physical activity during pregnancy reduces the likelihood of depression during pregnancy and after childbirth, benefiting both the pregnant woman and the foetus. However, most pregnant women are known to be inactive. The Pregnancy Physical Activity Questionnaire (PPAQ) analyses the level of physical activity of pregnant women. These data are correlated with the variable depression, for which the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy was used. Materials and Methods: The research employed a cross sectional study design on ninety-nine pregnant women. Results: The data on physical activity in relation to depression in those pregnant women who had not previously suffered from depression were 719.29 METS min/wk compared with 624.62 METS min/wk in those who had. And for pregnant women who suffered from depression at the time of the study, their physical activity was 698.25 METS min/wk, while those who did not suffer from depression reached 826.57 METS. Conclusions: Pregnant women without depression are much more active. A favourable employment situation or a high level of education is directly related to higher physical activity. Physical activity and higher energy expenditure occur at home, as opposed to activity carried out as transport, exercise or at work.

Identification of Players Controlling Meristem Arrest Downstream of the FRUITFULL-APETALA2 Pathway.

The end of the reproductive phase in monocarpic plants is determined by a coordinated arrest of all active meristems, a process known as global proliferative arrest (GPA). GPA is linked to the correlative control exerted by developing seeds and, possibly, the establishment of strong source-sink relationships. It has been proposed that the meristems that undergo arrest at the end of the reproductive phase behave at the transcriptomic level as dormant meristems, with low mitotic activity and high expression of abscisic acid response genes. Meristem arrest is also controlled genetically. In Arabidopsis (Arabidopsis thaliana), the MADS-box transcription factor FRUITFULL induces GPA by directly repressing genes of the APETALA2 (AP2) clade. The AP2 genes maintain shoot apical meristem (SAM) activity in part by keeping WUSCHEL expression active, but the mechanisms downstream of this pathway remain elusive. To identify target genes, we performed a transcriptomic analysis, inducing AP2 activity in meristems close to arrest. Our results suggest that AP2 controls meristem arrest by repressing genes related to axillary bud dormancy in the SAM and negative regulators of cytokinin signaling. In addition, our analysis indicates that genes involved in the response to environmental signals also respond to AP2, suggesting that it could modulate the end of flowering by controlling responses to both endogenous and exogenous signals. Our results support the previous observation that at the end of the reproductive phase the arrested SAM behaves as a dormant meristem, and they strongly support AP2 as a master regulator of this process.

Double nail of the second toe: A case report with sonographic and radiological correlation.

Double toenail is a rare abnormality that usually affects the fifth toe. It is considered as an inherited condition that may represent an incomplete form of polydactyly. Underlying bone abnormalities should be ruled out. We present a case of a double toenail of the second toe, a location that has not previously been described, with underlying bone involvement noted on ultrasound and plain films.

Head and neck squamous cell carcinoma in solid organ transplant recipients.

PURPOSE: Characterize head and neck squamous cell carcinomas in solid transplant recipients and compare outcomes with non-transplanted population. METHODS: We carried a retrospective cohort analysis in a tertiary care center in Madrid, Spain. The study reviews 26 cases of non-cutaneous HNSCC diagnosed in solid organ transplant recipients between 2000 and 2017. We select a cohort of 130 (1:5) non-transplanted patients among all non-transplanted patients diagnosed during the same period for comparison purposes, through hierarchical clustering analysis. Univariate, overall and specific survival analysis and multivariate Cox proportional hazards regression were used to evaluate our objectives. RESULTS: The overall risk of non-cutaneous HNSCC in solid transplant recipients was 7.2 cases per 1000. Alcohol abuse (p = 0.021) and upfront surgery (p = 0.019) were more likely to occur in transplanted patients. Age > 60 was an independent predictor of worse outcomes both for overall (HR = 2.4, p < 0.001) and specific (HR = 2.1, p = 0.012) survival. Transplant significantly worse overall survival (HR = 2.1, p = 0.012) but no statistical significant differences were observed on specific survival (p = 0.392). CONCLUSIONS: Solid organ transplant recipients have a higher risk of suffering non-cutaneous HNSCC. The higher mortality rate of these patients does not appear to be directly related to suffering from head and neck cancer, although it seems to contribute to developing other fatal complications in these fragile patients.

Testing the Contribution of Multi-Source Remote Sensing Features for Random Forest Classification of the Greater Amanzule Tropical Peatland.

Tropical peatlands such as Ghana's Greater Amanzule peatland are highly valuable ecosystems and under great pressure from anthropogenic land use activities. Accurate measurement of their occurrence and extent is required to facilitate sustainable management. A key challenge, however, is the high cloud cover in the tropics that limits optical remote sensing data acquisition. In this work we combine optical imagery with radar and elevation data to optimise land cover classification for the Greater Amanzule tropical peatland. Sentinel-2, Sentinel-1 and Shuttle Radar Topography Mission (SRTM) imagery were acquired and integrated to drive a machine learning land cover classification using a random forest classifier. Recursive feature elimination was used to optimize high-dimensional and correlated feature space and determine the optimal features for the classification. Six datasets were compared, comprising different combinations of optical, radar and elevation features. Results showed that the best overall accuracy (OA) was found for the integrated Sentinel-2, Sentinel-1 and SRTM dataset (S2+S1+DEM), significantly outperforming all the other classifications with an OA of 94%. Assessment of the sensitivity of land cover classes to image features indicated that elevation and the original Sentinel-1 bands contributed the most to separating tropical peatlands from other land cover types. The integration of more features and the removal of redundant features systematically increased classification accuracy. We estimate Ghana's Greater Amanzule peatland covers 60,187 ha. Our proposed methodological framework contributes a robust workflow for accurate and detailed landscape-scale monitoring of tropical peatlands, while our findings provide timely information critical for the sustainable management of the Greater Amanzule peatland.

Assessing and measuring financial sustainability model of the Spanish HIV HGM BioBank.

BACKGROUND: The Spanish HIV HGM BioBank is of great relevance for basic and clinical investigation, and for those groups trying to establish large networks focused on investigation on specific clinical problems. The collection of different types of samples from HIV-infected individuals is the beginning of the chain of translational investigation, starting in 2004 a prospective national HIV BioBank that expanded in 2009 a local node (HGM: Hospital Gregorio Marañón) for diverse pathologies and clinical networks, not only in adults but also in paediatric patients, becoming the Spanish HIV HGM BioBank. Our main objective is to find a general criteria and analytical tools to widespread its economic management to assure their sustainability and the future exploitation of the extreme high valuable biomaterial they custody. METHODS: The Spanish HIV HGM BioBank was created with the aim of contributing to advance understanding of different pathologies through the transfer, management, register, processing, cryopreservation and cession of biological material from patients, always for research purposes and under conditions that guarantee its usefulness in current studies and future research that may appear as knowledge evolves. In this study, we have developed a policy for financial control and recovery costs of the Spanish HIV HGM BioBank. RESULTS: Actually, Spanish HIV HGM BioBank guards 413,747 vials of 46,594 samples from 16,210 donors with various prospective longitudinal study type of samples. Interestingly, more than 7907 of these samples are now used in 28 national and international investigation projects and clinical trials. One of the objectives of this study is to develop an economic plan that you get future projects, design of acceptance or rejection keys, have internal investment limits, minimum recovery needs in short/medium term, deviation detection system and a register of capital recovery by period and type of service for the Spanish HIV HGM BioBank. CONCLUSION: Our model can help BioBanks that do not have a costs recovery model to design it, as well as to detect improves and functional revisions to those experienced in this field.

Ethyl alcohol threshold test: a fast, reliable and affordable olfactory Assessment tool for COVID-19 patients.

OBJECTIVE: COVID-19 patients may present mild symptoms. The identification of paucisymptomatic patients is paramount in order to interrupt the transmission chain of the virus. Olfactory loss could be one of those early symptoms which might help in the diagnosis of COVID-19 patients. In this study, we aim to develop and validate a fast, inexpensive, reliable and easy-to-perform olfactory test for the screening of suspected COVID-19 patients. STUDY DESIGN: Phase I was a case-control study and Phase II a transversal descriptive study. SUBJECTS AND METHODS: Olfaction was assessed with the ethyl alcohol threshold test and symptoms with visual analogue scales. The study was designed in two phases: In Phase I, we compared confirmed COVID-19 patients and healthy controls. In Phase II, patients with suspected COVID-19 infection referred for testing were studied. RESULTS: 275 participants were included in Phase I, 135 in Phase II. The ROC curve showed an AUC of 0.749 in Phase I, 0.737 in Phase II. The cutoff value which offered the highest amount of correctly classified patients was ≥ 2 (10% alcohol) for all age intervals. The odds ratio was 8.19 in Phase I, 6.56 in Phase II with a 75% sensitivity. When cases report normal sense of smell (VAS < 4), it misdiagnoses 57.89% of patients detected by the alcohol threshold test. CONCLUSION: The olfactory loss assessed with the alcohol threshold test has shown high sensitivity and odds ratio in both patients with confirmed COVID-19 illness and participants with suspected SARS-CoV-2 infection.

[Impact of frailty status on health and quality of life in Spanish older adults]. / Impacto del estatus de fragilidad sobre la salud y calidad de vida en personas mayores españolas.

OBJECTIVE: The aim of this study is to evaluate the predictive power of a latent measure of frailty based on the physical indicators proposed for the Survey of Health, Aging and Retirement in Europe (SHARE) on the quality of life and perceived health status in a representative sample of Spanish older adults. DESIGN: Descriptive cross-sectional study. SETTING: Spain. PARTICIPANTS: The sample was composed of 4,498 community-dwelling older Spanish adults aged 60 or over, extracted from wave six of SHARE. PRINCIPAL MEASUREMENTS: A structural equation model was used to define the frailty factor based on the five physical indicators proposed for SHARE (mobility, appetite, fatigue, activity, and strength), and test its effects on quality of life and perceived health status. RESULTS: Results showed an excellent fit of the model to the data (P<.001, CFI=.977, and SRMR=.041). Frailty factor explained 39.5% of the variance in quality of life and 61.6% of the variance in perceived health. CONCLUSIONS: The latent factor of frailty presented in this construct has an excellent fit to the data. The predictive power of frailty on the quality of life and perceived health in a sample of the Spanish population is highlighted.

Ultrasound Elastography Images in Vascular Anomalies.

Ultrasound elastography is an emerging imaging technique that provides an objective method to assess the relative or absolute stiffness of soft tissues. The authors have not found any description in the use of ultrasound elastography in vascular anomalies, and we want to share our experience in different cases with ultrasound elastography and its applications in these pathologies.

Psychometric properties of the Spanish version of the involvement evaluation questionnaire in caregivers of patients with borderline personality disorders.

The involvement evaluation questionnaire (IEQ) was created to evaluate the caregiver's experience of burden and the consequences of providing care to people with psychotic disorders. To date, the IEQ has not been validated with caregivers of people diagnosed with borderline personality disorder (BPD). The main objective of the study was to confirm the psychometric properties and factorial structure of the Spanish version of the IEQ in 151 caregivers of people with BPD, with an average age of 54.52 (SD = 9.91). Two models were tested by means of confirmatory factor analysis, following the original factor structure. The Models 1 and 2 displayed adequate fit, with comparative fit index and Tucker-Lewis index > 0.90 and root-mean-square root of approximation < 0.08; however, Model 2 was more parsimonious. The Cronbach's alphas are adequate, ranging from 0.70 to 0.85. The consequences of providing care to people with BPD had a low or moderate association with the Level of Expressed Emotion scores. IEQ scores of caregivers of people diagnosed with BPD with psychiatric comorbidity did not differ from those of caregivers of people diagnosed with BPD without psychiatric comorbidity. The IEQ has adequate psychometric properties and can be utilized to assess burden in caregivers of people with BPD.