Search

The aim of this study was to estimate genetic parameters and investigate the genomic background of scrotal circumference and semen parameters in the Italian Simmental bulls. Scrotal circumference, number of normal spermatozoa, ejaculate volume, spermatozoa motility, and total spermatozoa were measured on 622 bulls, of which 603 had genotypes for 42,141 SNP. Variance components of scrotal circumference were estimated with an animal model that included the fixed effects of birth year, animal age, and measurement method, and the random effects of day of measurement and animal. In the model for the other traits, the scrotal circumference was added as a covariate to account for its influence on the semen parameters. A genome-wide association study was carried out using the ssGBLUP-approach. Heritabilities ranged from 0.07 ± 0.05 (spermatozoa motility) to 0.50 ± 0.14 (scrotal circumference). A total of 13 SNP passed the Bonferroni correction threshold and the number of significantly associated markers ranged from 1 (ejaculate volume and spermatozoa motility) to 5 (total spermatozoa). Genes already associated with reproduction parameters were retrieved close to the significant SNP. Results of the present study gave preliminary insights about the genetic determinism of semen quality in Italian Simmental bulls.Highlights Low to moderate heritabilities were estimated for semen traits. Few markers were associated with the phenotypes, suggesting their polygenic determinism. Candidate genes already associated in literature with sperm traits were found.

Changes and disturbances to water diversity and quality are complex and multi-scale in space and time. Although in situ methods provide detailed point information on the condition of water bodies, they are of limited use for making area-based monitoring over time, as aquatic ecosystems are extremely dynamic. Remote sensing (RS) provides methods and data for the cost-effective, comprehensive, continuous and standardised monitoring of characteristics and changes in characteristics of water diversity and water quality from local and regional scales to the scale of entire continents. In order to apply and better understand RS techniques and their derived spectral indicators in monitoring water diversity and quality, this study defines five characteristics of water diversity and quality that can be monitored using RS. These are the diversity of water traits, the diversity of water genesis, the structural diversity of water, the taxonomic diversity of water and the functional diversity of water. It is essential to record the diversity of water traits to derive the other four characteristics of water diversity from RS. Furthermore, traits are the only and most important interface between in situ and RS monitoring approaches. The monitoring of these five characteristics of water diversity and water quality using RS technologies is presented in detail and discussed using numerous examples. Finally, current and future developments are presented to advance monitoring using RS and the trait approach in modelling, prediction and assessment as a basis for successful monitoring and management strategies.

ABSTRACT This study aimed to evaluate the in vitro gas production from three pearl millet cultivars submitted to four nitrogen levels. The treatments consisted of three pearl millet cultivars (ADR 500, ADR 7020, and LABH 70732) and four nitrogen levels (0, 50, 100, and 200 kg/ha), using urea as the nitrogen source. A 3 x 4 factorial experimental design, employing a randomized block setup, was used to assess both gas production and digestibility. No interaction was observed between nitrogen doses and fermentative parameters on in vitro gas production from the dry matter of pearl millet cultivars. Nitrogen had no impact on the dry matter content or chemical composition of the cultivars. Consistency prevailed in the chemical composition across the various cultivars, a trend that extended to the gas production rates for both soluble and insoluble contents. Notably, nitrogen fertilizer exerted an influence on the fermentation pattern of organic matter, gas production, and lag time for the cultivars. Nitrogen fertilization is advised solely for enhancing fermentative attributes in the case of the cultivar ADR 7020.

Abstract Providing an anodic potential in a bio‐electrochemical system to the obligate aerobe Pseudomonas putida enables anaerobic survival and allows the cells to overcome redox imbalances. In this setup, the bacteria could be exploited to produce chemicals via oxidative pathways at high yield. However, the absence of anaerobic growth and low carbon turnover rates remain as obstacles for the application of such an electro‐fermentation technology. Growth and carbon turnover start with carbon uptake into the periplasm and cytosol. P. putida KT2440 has three native transporting systems for glucose, each differing in energy and redox demand. This architecture previously led to the hypothesis that internal redox and energy constraints ultimately limit cytoplasmic carbon utilization in a bio‐electrochemical system. However, it remains largely unclear which uptake route is predominantly used by P. putida under electro‐fermentative conditions. To elucidate this, we created three gene deletion mutants of P. putida KT2440, forcing the cells to exclusively utilize one of the routes. When grown in a bio‐electrochemical system, the pathway mutants were heavily affected in terms of sugar consumption, current output and product formation. Surprisingly, however, we found that about half of the acetate formed in the cytoplasm originated from carbon that was put into the system via the inoculation biomass, while the other half came from the consumption of substrate. The deletion of individual sugar uptake routes did not alter significantly the secreted acetate concentrations among different strains even with different carbon sources. This means that the stoichiometry of the sugar uptake routes is not a limiting factor during electro‐fermentation and that the low rates might be caused by other reasons, for example energy limitations or a yet‐to‐be‐identified oxygen‐dependent regulatory mechanism.

One of the greatest challenges of our time is monitoring the rapid environmental changes taking place worldwide at both local and global scales. This requires easy-to-use and ready-to-implement tools and services to monitor and quantify aspects of bio- and geodiversity change and the impact of land use intensification using freely available and global remotely sensed data, and to derive remotely sensed indicators. Currently, there are no services for quantifying both raster- and vector-based indicators in a “compact tool”. Therefore, the main innovation of ESIS/Imalys is having a remote sensing (RS) tool that allows for RS data processing, data management, and continuous and discrete quantification and derivation of RS indicators in one tool. With the ESIS/Imalys project (Ecosystem Integrity Remote Sensing—Modelling and Service Tool), we try to present environmental indicators on a clearly defined and reproducible basis. The Imalys software library generates the RS indicators and remote sensing products defined for ESIS. This paper provides an overview of the functionality of the Imalys software library. An overview of the technical background of the implementation of the Imalys library, data formats and the user interfaces is given. Examples of RS-based indicators derived using the Imalys tool at pixel level and at zone level (vector level) are presented. Furthermore, the advantages and disadvantages of the Imalys tool are discussed in detail in order to better assess the value of Imalys for users and developers. The applicability of the indicators will be demonstrated through three ecological applications, namely: (1) monitoring landscape diversity, (2) monitoring landscape structure and landscape fragmentation, and (3) monitoring land use intensity and its impact on ecosystem functions. Despite the integration of large amounts of data, Imalys can run on any PC, as the processing and derivation of indicators has been greatly optimised. The Imalys source code is freely available and is hosted and maintained under an open source license. Complete documentation of all methods, functions and derived indicators can be found in the freely available Imalys manual. The user-friendliness of Imalys, despite the integration of a large amount of RS data, makes it another important tool for ecological research, modelling and application for the monitoring and derivation of ecosystem indicators from local to global scale.

The sustainable provision of ecological products and services, both natural and man-made, faces a substantial threat emanating from invasive plant species (IPS), which inflict considerable economic and ecological harm on a global scale. They are widely recognized as one of the primary drivers of global biodiversity decline and have become the focal point of an increasing number of studies. The integration of remote sensing (RS) and geographic information systems (GIS) plays a pivotal role in their detection and classification across a diverse range of research endeavors, emphasizing the critical significance of accounting for the phenological stages of the targeted species when endeavoring to accurately delineate their distribution and occurrences. This study is centered on this fundamental premise, as it endeavors to amass terrestrial data encompassing the phenological stages and spectral attributes of the specified IPS, with the overarching objective of ascertaining the most opportune time frames for their detection. Moreover, it involves the development and validation of a detection and classification algorithm, harnessing a diverse array of RS datasets, including satellite and unmanned aerial vehicle (UAV) imagery spanning the spectrum from RGB to multispectral and near-infrared (NIR). Taken together, our investigation underscores the advantages of employing an array of RS datasets in conjunction with the phenological stages, offering an economically efficient and adaptable solution for the detection and monitoring of invasive plant species. Such insights hold the potential to inform both present and future policymaking pertaining to the management of invasive species in agricultural and natural ecosystems.

Precision agriculture relies on understanding crop growth dynamics and plant responses to short-term changes in abiotic factors. In this technical note, we present and discuss a technical approach for cost-effective, non-invasive, time-lapse crop monitoring that automates the process of deriving further plant parameters, such as biomass, from 3D object information obtained via stereo images in the red, green, and blue (RGB) color space. The novelty of our approach lies in the automated workflow, which includes a reliable automated data pipeline for 3D point cloud reconstruction from dynamic scenes of RGB images with high spatio-temporal resolution. The setup is based on a permanent rigid and calibrated stereo camera installation and was tested over an entire growing season of winter barley at the Global Change Experimental Facility (GCEF) in Bad Lauchstädt, Germany. For this study, radiometrically aligned image pairs were captured several times per day from 3 November 2021 to 28 June 2022. We performed image preselection using a random forest (RF) classifier with a prediction accuracy of 94.2% to eliminate unsuitable, e.g., shadowed, images in advance and obtained 3D object information for 86 records of the time series using the 4D processing option of the Agisoft Metashape software package, achieving mean standard deviations (STDs) of 17.3–30.4 mm. Finally, we determined vegetation heights by calculating cloud-to-cloud (C2C) distances between a reference point cloud, computed at the beginning of the time-lapse observation, and the respective point clouds measured in succession with an absolute error of 24.9–35.6 mm in depth direction. The calculated growth rates derived from RGB stereo images match the corresponding reference measurements, demonstrating the adequacy of our method in monitoring geometric plant traits, such as vegetation heights and growth spurts during the stand development using automated workflows.

Plastic pollution is a global diffuse threat, especially considering its fragmentation into microplastics (MPs) and nanoplastics (NPs). Since the contamination of the aquatic environment is already well studied, most studies have now focused on the soil. Moreover, the number of studies on the exposure routes and toxic effects of MNPs in humans is continuously increasing. Although MNPs can cause inflammation, cytotoxicity, genotoxicity and immune toxicity in livestock animals, which can accumulate ingested/inhaled plastic particles and transfer them to humans through the food chain, research on this topic is still lacking. In considering farm animals as the missing link between soil/plant contamination and human health effects, this paper aims to describe their importance as carriers and vectors of MNP contamination. As research on this topic is in its early stages, there is no standard method to quantify the amount and the characteristics of MNPs in different matrices. Therefore, the creation of a common database where researchers can report data on MNP characteristics and quantification methods could be helpful for both method standardization and the future training of an AI tool for predicting the most abundant/dangerous polymer(s), thus supporting policy decisions to reduce plastic pollution and perfectly fitting with One Health principles.

Neuroblastoma (NB) is the most frequent extracranial solid childhood tumor. Despite advances in the understanding and treatment of this disease, the prognosis in cases of high-risk NB is still poor. 17q gain has been shown to be the most frequent genomic alteration in NB. However, the significance of this remains unclear because of its high frequency and association with other genetic modifications, particularly segmental chromosomal aberrations, 1p and 11q deletions, and MYCN amplification, all of which are also associated with a poor clinical prognosis. This work reviewed the evidence on the clinical and biological significance of 17q gain. It strongly supports the significance of 17q gain in the development of NB and its importance as a clinically relevant marker. However, it is crucial to distinguish between whole and partial chromosome 17q gains. The most important breakpoints appear to be at 17q12 and 17q21. The former distinguishes between whole and partial chromosome 17q gain; the latter is a site of IGF2BP1 and NME1 genes that appear to be the main oncogenes responsible for the functional effects of 17q gain.

State-of-the-art individual-atom tweezer platforms have relied on loading schemes based on spatially superimposing the tweezer array with a cloud of cold atoms created beforehand. Together with immanent atom loss, this dramatically limits the data rate, as the application sequence must be alternated with the time-consuming phases of magneto-optical trapping and laser cooling. We introduce a modular scheme built on an additional cold-atom reservoir and an array of buffer traps effectively decoupling cold-atom accumulation and single-atom supply from the quantum-register operation. For this purpose, we connect a microlens-based tweezer array to a cloud of laser-cooled atoms held in an auxiliary large-focus dipole trap by utilizing atom transport and buffer traps for dedicated single-atom supply. We demonstrate deterministic loading of a hexagonal target structure with atoms solely originating from the reservoir trap. The results facilitate increased data rates and unlock a path to continuous operation of individual-atom tweezer arrays in quantum science, making use of discrete functional modules, operated in parallel and spatially separated.

O objetivo deste estudo foi avaliar a inclusão do extrato hidroalcoólico de rosela (Hibiscus sabdariffa) em dietas do peixe Mato Grosso (Hyphessobrycon eques). Foram utilizados 120 peixes (0,51± 0,06 g), que foram distribuídos aleatoriamente em 12 aquários de polietileno de 20L, em sistema de recirculação de água, com a densidade de estocagem de 10 peixes por aquário. Os peixes foram alimentados por 21 dias com uma dieta (40,88% PB e 4374,8 Kcal kg-1), acrescida de extrato hidroalcoólico de rosela - EHR (controle; 0,12; 0,25 e 0,50 mg de EHR/kg de ração). A inclusão de concentração de 0,25 e 0,50 EHR/kg, promoveu uma melhora nos índices zootécnicos, comprimento padrão e eficiência alimentar. Os peixes apresentaram alteração de croma a*(tonalidades de verde e vermelho), entretanto, não houve aumento de intensidade em relação à luminosidade croma b* (tonalidades de azul e amarelo). A utilização de 0,25 e 0,50 EHR/kg refletiu em diminuição da atividade das enzimas AST e ALT. Observou-se o aumento da atividade catalase em concentrações com maiores índices de extratos hidroalcoólicos de rosela na dieta. O extrato hidroalcoólico de rosela é eficiente na alimentação de peixe Mato Grosso na concentração de 0,50 mg EHR/kg.

Changes and disturbances to water diversity and quality are complex and multi-scale in space and time. Although in situ methods provide detailed point information on the condition of water bodies, they are of limited use for making area-based monitoring over time, as aquatic ecosystems are extremely dynamic. Remote sensing (RS) provides methods and data for the cost-effective, comprehensive, continuous and standardised monitoring of characteristics and changes in characteristics of water diversity and water quality from local and regional scales to the scale of entire continents. In order to apply and better understand RS techniques and their derived spectral indicators in monitoring water diversity and quality, this study defines five characteristics of water diversity and quality that can be monitored using RS. These are the diversity of water traits, the diversity of water genesis, the structural diversity of water, the taxonomic diversity of water and the functional diversity of water. It is essential to record the diversity of water traits to derive the other four characteristics of water diversity from RS. Furthermore, traits are the only and most important interface between in situ and RS monitoring approaches. The monitoring of these five characteristics of water diversity and water quality using RS technologies is presented in detail and discussed using numerous examples. Finally, current and future developments are presented to advance monitoring using RS and the trait approach in modelling, prediction and assessment as a basis for successful monitoring and management strategies. [ABSTRACT FROM AUTHOR]

Abstract Non-alcoholic fatty liver disease (NAFLD) is the most frequent liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH), which is characterized by triglyceride accumulation, inflammation, and fibrosis. No pharmacological agents are currently approved to treat these conditions, but it is clear now that modulation of lipid synthesis and autophagy are key biological mechanisms that could help reduce or prevent these liver diseases. The folliculin (FLCN) protein has been recently identified as a central regulatory node governing whole body energy homeostasis, and we hypothesized that FLCN regulates highly metabolic tissues like the liver. We thus generated a liver specific Flcn knockout mouse model to study its role in liver disease progression. Using the methionine- and choline-deficient diet to mimic liver fibrosis, we demonstrate that loss of Flcn reduced triglyceride accumulation, fibrosis, and inflammation in mice. In this aggressive liver disease setting, loss of Flcn led to activation of transcription factors TFEB and TFE3 to promote autophagy, promoting the degradation of intracellular lipid stores, ultimately resulting in reduced hepatocellular damage and inflammation. Hence, the activity of FLCN could be a promising target for small molecule drugs to treat liver fibrosis by specifically activating autophagy. Collectively, these results show an unexpected role for Flcn in fatty liver disease progression and highlight new potential treatment strategies.

There is little information on the actual use of early synthetic organic pigments (SOPs) in art objects, especially those from before 1950. Their presence can, however, pose a challenge to conservation because their chemical composition, as well as their lightfastness and sensitivity to solvents, are often unknown. Here, a study on the non-invasive identification of SOPs in historic pre-1950 varnished paint-outs from artists’ materials manufacturer Royal Talens is presented. The paints were analysed using a handheld Raman device. Spectra were evaluated by recording the spectra of the same samples with a benchtop instrument. This study demonstrated that the identification of SOPs in varnished oil paints with a non-invasive approach is possible and rather straightforward. The handheld Raman device allowed us to identify fourteen SOPs from eight pigment classes. Besides the occurrence of expected and the known SOPs of this time period, there were also some surprising results, like the detection of the triarylcarbonium pigments PG2 and PB8, and the monoazo Mordant Yellow 1.

Testicular tissue cryopreservation is the only option of fertility preservation in prepubertal boys. While it is considered experimental, since procedures to obtain mature spermatozoa from prepubertal testicular tissue are still under development, testicular tissue cryopreservation programs have emerged worldwide. Our aim was to study the feasibility and safety of a program of testicular tissue cryopreservation in prepubertal and adolescent boys facing gonadotoxic treatment in three University hospitals in Switzerland. Testicular tissue cryopreservation was accepted by 90% of families, with a total of 35 patients included. The average patient age was 8.5 years (range 7 months to 18.5 years). Malignancies were the most common diagnosis (31 patients, 88.6%) with 16 (45.7%) solid tumors and 15 (42.9%) hematological malignancies. Four (11.4%) patients had a benign condition. The main indication for testicular tissue cryopreservation was conditioning for hematologic stem cell transplantation (25 patients, 71.4%). Testicular tissue was cryopreserved according to the freezing protocol of Louvain Catholic University (Belgium), which includes either only immature testicular tissue freezing, or mature and immature testicular tissue freezing depending on the age of the patient and the presence or absence of haploid cells. The median number of spermatogonia per tubule cross-section was 2 (range 0–6) and spermatozoa were found in only one patient. Tumoral cells were found in one testicular biopsy of a leukemic patient. There were two minor adverse events and none of them required medical treatment or surgical revision. Five patients died during follow-up. Our data demonstrate the feasibility and safety of a program of testicular tissue cryopreservation coordinated by a multidisciplinary team of fertility preservation. Despite the experimental aspect of the procedure, the acceptation rate was high, which highlights the willingness of families and patients to participate in testicular tissue cryopreservation.

Abstract Neuroblastoma is the most common extra-cranial solid tumor in children, representing approximately 8% of all malignant childhood tumors and 15% of pediatric cancer-related deaths. Recent sequencing and transcriptomics studies have demonstrated the RAS-MAPK pathway’s contribution to the development and progression of neuroblastoma. This review compiles up-to-date evidence of this pathway’s involvement in neuroblastoma. We discuss the RAS-MAPK pathway’s general functioning, the clinical implications of its deregulation in neuroblastoma, and current promising therapeutics targeting proteins involved in signaling.

AIMS OF THE STUDY: Although the 5-year survival for pediatric cancer in Switzerland today is over 85%, two thirds of the survivors will develop chronic health conditions due to the disease or to the toxicity of treatments. In this context, a long-term personalized follow-up program (LTFU program), was set up at the University Hospitals of Geneva (HUG) since 2015. We aimed to describe this program, more particularly the specialized follow-ups set up, the cumulative burden of the chronic health conditions, and finally assess the satisfaction of patients and/or their parents with it. METHODS: A monocentric retrospective study was performed where data on follow-ups and chronic health conditions were collected from medical charts of people who had childhood cancer and who participated in the LTFU program. Chronic health conditions were classified and graded in severity with the Common Terminology Criteria of Adverse Events (CTCAE) classification, version 5.0. This study was completed by a satisfaction survey among patients and/or their parents. RESULTS: Out of 83 eligible patients, 51 (61.4%) accepted to participate, with an average age of 17.4 years (range, 10 to 35) at the time of study. Mean delay since end of treatment was 9.8 years (range: 4.5–31). The prevalence of any chronic health condition is 82.3%, 43.1% for having 1 or 2 chronic health conditions and 39.2% for having more than 3 chronic health conditions. The total number of Grade CTCAE 1–4 chronic health conditions was 118 for the 51 participants, with a mean of 2.3 (range, 0 to 7) disorders per patient. The most frequently affected systems were neurological (14.4%), musculoskeletal (13.6%), endocrine (9.3%) and renal (9.3%) systems. Sarcoma, central nervous system tumors and neuroblastoma were the diagnoses associated with the highest average number of chronic health conditions. Among the 118 questionnaires sent to patients and/or parents, we received 82 (69.5%) responses. The level of satisfaction was good to excellent for more than 90% of the participants, for all the items evaluated. CONCLUSIONS: Childhood cancer survivors present a significant number of chronic health conditions, confirming the need for appropriate long-term, multidisciplinary and patient-specific medical follow-up based on the primary diagnosis and therapies received. Moreover, the LTFU program at the HUG was highly appreciated by patients and/or their parents and this motivates its permanent conduct.

Pollution due to microplastics and nanoplastics is one of the major environmental issues of the last decade and represents a growing threat to human and animal health. In aquatic species, there is a large amount of information regarding the perturbation of marine organisms; instead, there are only a few studies focusing on the pathophysiological consequences of an acute and chronic exposure to micro- and nanoplastics in mammalian systems, especially on the reproductive system. There are several studies that have described the damage caused by plastic particles, including oxidative stress, apoptosis, inflammatory response, dysregulation of the endocrine system and accumulation in various organs. In addition to this, microplastics have recently been found to influence the evolution of microbial communities and increase the gene exchange, including antibiotic and metal resistance genes. Special attention must be paid to farm animals, because they produce food such as milk, eggs and meat, with the consequent risk of biological amplification along the food chain. The results of several studies indicate that there is an accumulation of microplastics and nanoplastics in human and animal tissues, with several negative effects, but all the effects in the body have not been ascertained, especially considering the long-term consequences. This review provides an overview of the possible adverse effects of the exposure of livestock to micro- and nanoplastics and assesses the potential risks for the disruption of reproductive physiological functions.

One of the greatest challenges of our time is monitoring the rapid environmental changes taking place worldwide at both local and global scales. This requires easy-to-use and ready-to-implement tools and services to monitor and quantify aspects of bio- and geodiversity change and the impact of land use intensification using freely available and global remotely sensed data, and to derive remotely sensed indicators. Currently, there are no services for quantifying both raster- and vector-based indicators in a "compact tool". Therefore, the main innovation of ESIS/Imalys is having a remote sensing (RS) tool that allows for RS data processing, data management, and continuous and discrete quantification and derivation of RS indicators in one tool. With the ESIS/Imalys project (Ecosystem Integrity Remote Sensing—Modelling and Service Tool), we try to present environmental indicators on a clearly defined and reproducible basis. The Imalys software library generates the RS indicators and remote sensing products defined for ESIS. This paper provides an overview of the functionality of the Imalys software library. An overview of the technical background of the implementation of the Imalys library, data formats and the user interfaces is given. Examples of RS-based indicators derived using the Imalys tool at pixel level and at zone level (vector level) are presented. Furthermore, the advantages and disadvantages of the Imalys tool are discussed in detail in order to better assess the value of Imalys for users and developers. The applicability of the indicators will be demonstrated through three ecological applications, namely: (1) monitoring landscape diversity, (2) monitoring landscape structure and landscape fragmentation, and (3) monitoring land use intensity and its impact on ecosystem functions. Despite the integration of large amounts of data, Imalys can run on any PC, as the processing and derivation of indicators has been greatly optimised. The Imalys source code is freely available and is hosted and maintained under an open source license. Complete documentation of all methods, functions and derived indicators can be found in the freely available Imalys manual. The user-friendliness of Imalys, despite the integration of a large amount of RS data, makes it another important tool for ecological research, modelling and application for the monitoring and derivation of ecosystem indicators from local to global scale. [ABSTRACT FROM AUTHOR]

Ataxia-telangiectasia (A-T) is a neurodegenerative and primary immunodeficiency disorder (PID) characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, progressive respiratory failure, and an increased risk of malignancies. It demands specialized care tailored to the individual patient’s needs. Besides the classical ataxia-telangiectasia (classical A-T) phenotype, a variant phenotype (variant A-T) exists with partly overlapping but some distinctive disease characteristics. Here we present a case series of 6 patients with classical A-T and variant A-T, which illustrates the phenotypic variability of A-T that can present in childhood with prominent extrapyramidal features, with or without cerebellar ataxia. We report the clinical data, together with a detailed genotype description, immunological analyses, and related expression of the ATM protein. We show that the presence of some residual ATM kinase activity leads to the clinical phenotype variant A-T that differs from the classical A-T. Our data illustrate that the diagnosis of the variant form of A-T can be delayed and difficult, while early recognition of the variant form as well as the classical A-T is a prerequisite for providing a correct prognosis and appropriate rehabilitation and support, including the avoidance of diagnostic X-ray procedures, given the increased risk of malignancies and the higher risk for side effects of subsequent cancer treatment.

Summary: Internalized and ubiquitinated signaling receptors are silenced by their intraluminal budding into multivesicular bodies aided by the endosomal sorting complexes required for transport (ESCRT) machinery. HD-PTP, an ESCRT protein, forms complexes with ESCRT-0, -I and -III proteins, and binds to Endofin, a FYVE-domain protein confined to endosomes with poorly understood roles. Using proximity biotinylation, we showed that Endofin forms a complex with ESCRT constituents and Endofin depletion increased integrin α5-and EGF-receptor plasma membrane density and stability by hampering their lysosomal delivery. This coincided with sustained receptor signaling and increased cell migration. Complementation of Endofin- or HD-PTP-depleted cells with wild-type Endofin or HD-PTP, but not with mutants harboring impaired Endofin/HD-PTP association or cytosolic Endofin, restored EGFR lysosomal delivery. Endofin also promoted Hrs indirect interaction with HD-PTP. Jointly, our results indicate that Endofin is required for HD-PTP and ESCRT-0 interdependent sorting of ubiquitinated transmembrane cargoes to ensure efficient receptor desensitization and lysosomal delivery.

The objectives of the study aimed to evaluate the effect of weather conditions and scrotal circumference (SC) on standard semen characteristics of Italian Simmental young bulls (n = 577), all raised in the same performance station and sampled by the artificial vagina (AV) method. Considering the increasing SC, the results showed a significant increase in quantitative semen parameters (p < 0.05 and p < 0.0001, for sperm concentration and total number of spermatozoa, respectively); for every extra centimeter of SC, 17.5 × 106 spermatozoa/mL and 0.102 × 109 of total spermatozoa were produced. The age of the animal at semen collection (395 and 465 days) had similar positive effects. The effect of the average temperature humidity index (THI limits ≤ 40 and ≥70) in the previous 60, 30, and 10 days before the semen collection was also considered. Sixty days before the semen collection, the increasing THI increased both primary (p < 0.0001) and secondary (p < 0.0001) abnormalities while the percentage of morphologically normal spermatozoa decreased (p < 0.0001). Thirty and ten days before collection, the same effect on morphological traits was maintained, but total and progressive motility was also influenced (p < 0.01) with an unexpected increasing pattern. Thus, environmental conditions can influence semen quality during the entire spermatogenesis and results can guide future research on this breed.

Folliculin (FLCN) is a tumor suppressor gene responsible for the inherited Birt-Hogg-Dubé (BHD) syndrome, which affects kidneys, skin and lungs. FLCN is a highly conserved protein that forms a complex with folliculin interacting proteins 1 and 2 (FNIP1/2). Although its sequence does not show homology to known functional domains, structural studies have determined a role of FLCN as a GTPase activating protein (GAP) for small GTPases such as Rag GTPases. FLCN GAP activity on the Rags is required for the recruitment of mTORC1 and the transcriptional factors TFEB and TFE3 on the lysosome, where mTORC1 phosphorylates and inactivates these factors. TFEB/TFE3 are master regulators of lysosomal biogenesis and function, and autophagy. By this mechanism, FLCN/FNIP complex participates in the control of metabolic processes. AMPK, a key regulator of catabolism, interacts with FLCN/FNIP complex. FLCN loss results in constitutive activation of AMPK, which suggests an additional mechanism by which FLCN/FNIP may control metabolism. AMPK regulates the expression and activity of the transcriptional cofactors PGC1α/β, implicated in the control of mitochondrial biogenesis and oxidative metabolism. In this review, we summarize our current knowledge of the interplay between mTORC1, FLCN/FNIP, and AMPK and their implications in the control of cellular homeostasis through the transcriptional activity of TFEB/TFE3 and PGC1α/β. Other pathways and cellular processes regulated by FLCN will be briefly discussed.

Simple Summary: Neuroblastoma (NB) is the most frequent solid extracranial tumor in children and the most frequently diagnosed cancer during infancy. A genetic modification, a gain of 17q chromosome arm, is the most common modification in neuroblastoma. Substantial research has been performed on 17q's role in neuroblastoma development and its clinical significance. This paper aims to make a comprehensive review of this evidence. The main findings of the review are: (1) current knowledge supports that 17q gain is involved in the development of neuroblastoma and (2) 17q gain is an important clinical marker independently and in association with other genetic modifications. Neuroblastoma (NB) is the most frequent extracranial solid childhood tumor. Despite advances in the understanding and treatment of this disease, the prognosis in cases of high-risk NB is still poor. 17q gain has been shown to be the most frequent genomic alteration in NB. However, the significance of this remains unclear because of its high frequency and association with other genetic modifications, particularly segmental chromosomal aberrations, 1p and 11q deletions, and MYCN amplification, all of which are also associated with a poor clinical prognosis. This work reviewed the evidence on the clinical and biological significance of 17q gain. It strongly supports the significance of 17q gain in the development of NB and its importance as a clinically relevant marker. However, it is crucial to distinguish between whole and partial chromosome 17q gains. The most important breakpoints appear to be at 17q12 and 17q21. The former distinguishes between whole and partial chromosome 17q gain; the latter is a site of IGF2BP1 and NME1 genes that appear to be the main oncogenes responsible for the functional effects of 17q gain. [ABSTRACT FROM AUTHOR]

Copyright of Romanitas: Revista de Estudos Greco-Latinas is the property of Universidade Federal do Espirito Santo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background Neuroblastoma is the most common extracranial solid tumor in children. This cancer has a low frequency of TP53 mutations and its downstream pathway is usually intact. This study assessed the efficacy of the p53 activator, PRIMA-1MET, in inducing neuroblastoma cell death. Methods CellTiter 2.0 was used to study susceptibility and specificity of NB cell lines to PRIMA-1MET. Real-time PCR and western blot were used to assess the most common p53 transactivation targets. Induction of p53 and Noxa, and inhibition of Cas3/7, were used to assess impact on cell death after PRIMA-1MET treatment. Flow cytometry was used to analyze cell cycle phase and induction of apoptosis, reactive oxygen species, and the collapse of mitochondrial membrane potential. Results Neuroblastoma cell lines were at least four times more susceptible to PRIMA-1MET than were primary fibroblasts and keratinocyte cell lines. PRIMA-1MET induced cell death rapidly and in all cell cycle phases. Although PRIMA-1MET activated p53 transactivation activity, p53’s role is likely limited because its main targets remained unaffected, whereas pan-caspase inhibitor demonstrated no ability to prevent cell death. PRIMA-1MET induced oxidative stress and modulated the methionine/cysteine/glutathione axis. Variations of MYCN and p53 modulated intracellular levels of GSH and resulted in increased/decreased sensitivity of PRIMA-1MET. PRIMA-1MET inhibited thioredoxin reductase, but the effect of PRIMA-1MET was not altered by thioredoxin inhibition. Conclusions PRIMA-1MET could be a promising new agent to treat neuroblastoma because it demonstrated good anti-tumor action. Although p53 is involved in PRIMA-1MET-mediated cell death, our results suggest that direct interaction with p53 has a limited role in neuroblastoma but rather acts through modulation of GSH levels.

A growing body of literature suggests a close link between olfaction and social expertise. The current study examines whether mentalizing skills are related to olfactory discrimination performance. In order to assess their mentalizing ability, 21 women and 20 men completed the “Reading the Mind in the Eyes” test (RMET). Here, the participants have to infer other persons’ mental state from photographs of eye regions. Odor discrimination was assessed using the “Düsseldorf Odour Discrimination Test” (DODT). The DODT consists of 15 items, each containing mixtures of four monomolecular substances. Within each item, two bottles contain the same mixing ratio, while the third contains the reversed mixing ratio. The participants had to identify the deviating odor. Women’s expertise in mentalizing (RMET score) is strongly related to olfactory discrimination performance (DODT score): The better women are in mentalizing, the better their performance in olfactory discrimination (rho = 0.572, p = 0.042, Bonferroni-corrected). Men’s mentalizing capability was unrelated to olfactory discrimination (rho = −0.117, p > 0.999, Bonferroni-corrected). The current results suggest that the social skill of mentalizing might underly the link between olfaction and social integration, at least in women, and are discussed with regard to the social nature of human olfaction.

Remote sensing (RS) enables a cost-effective, extensive, continuous and standardized monitoring of traits and trait variations of geomorphology and its processes, from the local to the continental scale. To implement and better understand RS techniques and the spectral indicators derived from them in the monitoring of geomorphology, this paper presents a new perspective for the definition and recording of five characteristics of geomorphodiversity with RS, namely: geomorphic genesis diversity, geomorphic trait diversity, geomorphic structural diversity, geomorphic taxonomic diversity, and geomorphic functional diversity. In this respect, geomorphic trait diversity is the cornerstone and is essential for recording the other four characteristics using RS technologies. All five characteristics are discussed in detail in this paper and reinforced with numerous examples from various RS technologies. Methods for classifying the five characteristics of geomorphodiversity using RS, as well as the constraints of monitoring the diversity of geomorphology using RS, are discussed. RS-aided techniques that can be used for monitoring geomorphodiversity in regimes with changing land-use intensity are presented. Further, new approaches of geomorphic traits that enable the monitoring of geomorphodiversity through the valorisation of RS data from multiple missions are discussed as well as the ecosystem integrity approach. Likewise, the approach of monitoring the five characteristics of geomorphodiversity recording with RS is discussed, as are existing approaches for recording spectral geomorhic traits/ trait variation approach and indicators, along with approaches for assessing geomorphodiversity. It is shown that there is no comparable approach with which to define and record the five characteristics of geomorphodiversity using only RS data in the literature. Finally, the importance of the digitization process and the use of data science for research in the field of geomorphology in the 21st century is elucidated and discussed.

Forum on conspiracy theories as narrative phenomenon.

Growing tumors exist in metabolically compromised environments that require activation of multiple pathways to scavenge nutrients to support accelerated rates of growth. The folliculin (FLCN) tumor suppressor complex (FLCN, FNIP1, FNIP2) is implicated in the regulation of energy homeostasis via 2 metabolic master kinases: AMPK and mTORC1. Loss-of-function mutations of the FLCN tumor suppressor complex have only been reported in renal tumors in patients with the rare Birt-Hogg-Dube syndrome. Here, we revealed that FLCN, FNIP1, and FNIP2 are downregulated in many human cancers, including poor-prognosis invasive basal-like breast carcinomas where AMPK and TFE3 targets are activated compared with the luminal, less aggressive subtypes. FLCN loss in luminal breast cancer promoted tumor growth through TFE3 activation and subsequent induction of several pathways, including autophagy, lysosomal biogenesis, aerobic glycolysis, and angiogenesis. Strikingly, induction of aerobic glycolysis and angiogenesis in FLCN-deficient cells was dictated by the activation of the PGC-1[alpha]/HIF-1[alpha] pathway, which we showed to be TFE3 dependent, directly linking TFE3 to Warburg metabolic reprogramming and angiogenesis. Conversely, FLCN overexpression in invasive basal-like breast cancer models attenuated TFE3 nuclear localization, TFE3-dependent transcriptional activity, and tumor growth. These findings support a general role of a deregulated FLCN/TFE3 tumor suppressor pathway in human cancers., Introduction Breast cancer is the first leading cause of cancer deaths in women worldwide, with thousands dying from the disease each year (1). Gene expression profiling classifies human breast cancers [...]

Der Artikel untersucht am Beispiel von Helmut Kraussers 2003 erschienenem Roman UC die Auseinandersetzung mit der „Episteme Netz“ (Hartmut Böhme) in der deutschsprachigen Gegenwartsliteratur. Gezeigt wird, wie in neueren Romanen Figuren des Netzes und der Vernetzung globalisierungskritisch gewendet werden, indem sie mit Symptomen der Entortung und des Identitätsverlustes assoziiert werden. Im Zentrum der Analyse steht das in vielen neueren Romanen strukturbildende Konzept einer netzförmigen Zeit, das eine Vielzahl sich gegenseitig ausschließender, aber dennoch gleichberechtigter Chronologien nebeneinander existieren lässt. Das Motiv des Zeitnetzes verweist dabei auf Werke einiger Klassiker der Postmoderne wie Jorge Luis Borges und Vladimir Nabokov, deren literarästhetische Konzepte von Krausser aufgenommen und vor dem Hintergrund einer veränderten globalen Lebenswirklichkeit problematisiert werden.