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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.

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.

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.

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.

Reactive oxygen species (ROS) are continuously produced as a by-product of mitochondrial metabolism and eliminated via antioxidant systems. Regulation of mitochondrially produced ROS is required for proper cellular function, adaptation to metabolic stress, and bypassing cellular senescence. Here, we report non-canonical regulation of the cellular energy sensor AMP-activated protein kinase (AMPK) by mitochondrial ROS (mROS) that functions to maintain cellular metabolic homeostasis. We demonstrate that mitochondrial ROS are a physiological activator of AMPK and that AMPK activation triggers a PGC-1α-dependent antioxidant response that limits mitochondrial ROS production. Cells lacking AMPK activity display increased mitochondrial ROS levels and undergo premature senescence. Finally, we show that AMPK-PGC-1α-dependent control of mitochondrial ROS regulates HIF-1α stabilization and that mitochondrial ROS promote the Warburg effect in cells lacking AMPK signaling. These data highlight a key function for AMPK in sensing and resolving mitochondrial ROS for stress resistance and maintaining cellular metabolic balance.

Understanding the relationship between land use and land cover and thermal environment has recently become an emerging issue for urban planners and policy makers. We chose Belgrade, as a case study, to present a cost- and time-effective framework for monitoring spatiotemporal changes of green spaces in relation to the land surface temperature (LST). Time series analysis was performed using Landsat 5 TM and Landsat 8 OLI/TIRS imagery from 1991 to 2019 with an approximate 5-year interval (18 images in total). Spectral vegetation indices and supervised land cover classifications were used to examine changes of green spaces. The results showed a fluctuating trend of the normalized difference vegetation index (NDVI) and the normalized difference water index (NDWI). The highest values were recorded in 2019, indicating vegetation recovery in the last decade. A significant positive correlation was determined between the spectral vegetation indices and the amount of precipitation during growing season. The land cover classification showed that the share of vegetated and bare land decreased by 11.74% during the study period. The most intensive conversion of green and bare land into built-up land cover occurred in the first decade (1991–2000). To assess spatiotemporal changes in the LST, Landsat Collection 2 Surface Temperature products were used. We found a negative correlation between change in the spectral vegetation indices and change in the LST. This indicates that the reduction in vegetation was associated with an increase in the LST. The municipalities that were the most affected in each decade were also identified with our framework. The findings of this study are of great relevance for actions targeting an improvement in urban thermal comfort and climate resilience.

The current study examines neural responses to satiety- and fasting-related volatiles and their effect on the processing of body shapes. Axillary sweat was sampled with cotton pads from 10 individuals after 12 h of fasting, and after having consumed a standard breakfast. Pure cotton pads served as the control. The chemosensory stimuli were presented to 20 participants (via a constant-flow olfactometer) exclusively, and additionally as context to images of overweight and underweight avatars. EEG was recorded (61 electrodes), and chemosensory (CSERPs; P1, N1, P2, P3) and visual event-related potentials (VERPs; N1, P2, P3a, P3b) were analyzed. The amplitudes of all positive CSERP components differed more strongly from cotton in response to chemosensory satiety cues as compared to fasting cues (P1: p = 0.023, P2: p = 0.083, P3: p = 0.031), paralleled by activity within the middle frontal and temporal gyrus. Overweight compared to underweight body shapes tended to elicit larger VERP P2 amplitudes (p = 0.068), and chemosensory satiety cues amplified the VERP amplitudes in response to any body shape (P2, P3a, P3b; all ps ≤ 0.017) as compared to the cotton control. The results indicate that chemosensory satiety cues transmit complex social information, overriding the processing of analogous visual input.

Abstract In humans, stress can be contagiously transmitted via chemosignals on a subconscious level. This study investigates how pregnancy affects neural responses to anxiety chemosignals. Using cotton pads, 28 men donated axillary sweat immediately before an academic examination (anxiety sweat) and during ergometer training (control). Via a constant-flow olfactometer, samples were presented (oddball paradigm) to 12 non-pregnant (NP) women, 14 women in their first (T1), and 18 in their third (T3) trimester of pregnancy. Chemosensory event-related potentials and current source densities (CSD) were analysed (60 electrode setup). Compared to NP-women, pregnant women display diminished evaluative processing of the sweat samples (targets; P3-1/ P3-2 amplitudes) and delayed evaluative processing of the anxiety sweat (targets; P3-2 latency). T3-women show attenuated early processing (targets; N1 amplitude) compared to NP-women, and reduced evaluative processing compared to T1-women (standards; P3-2 amplitude). CSDs (P3-1/ P3-2 latency ranges) reveal that T1- and T3-women show an atypical activation distribution to anxiety sweat. Most participants were unable to detect the sweat samples (anxiety sweat: 79.5%, sport sweat 88.6%). The results demonstrate that the processing of anxiety chemosignals progressively vanishes during pregnancy. This effect is likely to occur without any cognitive control.

Abstract Deletion of the long arm of chromosome 11 (11q deletion) is one of the most frequent events that occur during the development of aggressive neuroblastoma. Clinically, 11q deletion is associated with higher disease stage and decreased survival probability. During the last 25 years, extensive efforts have been invested to identify the precise frequency of 11q aberrations in neuroblastoma, the recurrently involved genes, and to understand the molecular mechanisms of 11q deletion, but definitive answers are still unclear. In this review, it is our intent to compile and review the evidence acquired to date on 11q deletion in neuroblastoma.

Summary: TFEB and TFE3 are transcriptional regulators of the innate immune response, but the mechanisms regulating their activation upon pathogen infection are poorly elucidated. Using C. elegans and mammalian models, we report that the master metabolic modulator 5′-AMP-activated protein kinase (AMPK) and its negative regulator Folliculin (FLCN) act upstream of TFEB/TFE3 in the innate immune response, independently of the mTORC1 signaling pathway. In nematodes, loss of FLCN or overexpression of AMPK confers pathogen resistance via activation of TFEB/TFE3-dependent antimicrobial genes, whereas ablation of total AMPK activity abolishes this phenotype. Similarly, in mammalian cells, loss of FLCN or pharmacological activation of AMPK induces TFEB/TFE3-dependent pro-inflammatory cytokine expression. Importantly, a rapid reduction in cellular ATP levels in murine macrophages is observed upon lipopolysaccharide (LPS) treatment accompanied by an acute AMPK activation and TFEB nuclear localization. These results uncover an ancient, highly conserved, and pharmacologically actionable mechanism coupling energy status with innate immunity. : El-Houjeiri et al. show that loss of FLCN or pharmacological activation of AMPK induces TFEB/TFE3-dependent pro-inflammatory cytokine expression and phagocytosis in macrophages and confers pathogen resistance in C. elegans. These results uncover an ancient, highly conserved, and pharmacologically actionable mechanism coupling energy status to innate immunity. Keywords: TFEB, TFE3, FLCN, AMPK, innate immune response, pathogen resistance, autophagy, lysosomal biogenesis, phagocytosis

Reduction of mu activity within the EEG is an indicator of cognitive empathy and can be generated in response to visual depictions of others in pain. The current study tested whether this brain response can be modulated by an auditory and a chemosensory context. Participants observed pictures of painful and non-painful actions while pain associated and neutral exclamations were presented (Study 1, N = 30) or while chemosensory stimuli were presented via a constant flow olfactometer (Study 2, N = 22). Chemosensory stimuli were sampled on cotton pads while donors participated in a simulated job interview (stress condition) or cycled on a stationary bike (sport condition). Pure cotton was used as a control. The social chemosignals could not be detected as odors. Activity within the 8–13 Hz band at electrodes C3, C4 (mu activity) and electrodes O1, O2 (alpha-activity) was calculated using Fast-Fourier-Transformation (FFT). As expected, suppression of power in the 8–13 Hz band was stronger when painful as compared to non-painful actions were observed (Study 1, p = 0.020; Study 2, p = 0.005). In addition, as compared to the neutral auditory and chemosensory context, painful exclamations (Study 1, p = 0.039) and chemosensory stress signals (Study 2, p = 0.014) augmented mu-/alpha suppression also in response to non-painful pictures. The studies show that processing of social threat-related information is not dominated by visual information. Rather, cognitive appraisal related to empathy can be affected by painful exclamations and subthreshold chemosensory social information.

The status, changes, and disturbances in geomorphological regimes can be regarded as controlling and regulating factors for biodiversity. Therefore, monitoring geomorphology at local, regional, and global scales is not only necessary to conserve geodiversity, but also to preserve biodiversity, as well as to improve biodiversity conservation and ecosystem management. Numerous remote sensing (RS) approaches and platforms have been used in the past to enable a cost-effective, increasingly freely available, comprehensive, repetitive, standardized, and objective monitoring of geomorphological characteristics and their traits. This contribution provides a state-of-the-art review for the RS-based monitoring of these characteristics and traits, by presenting examples of aeolian, fluvial, and coastal landforms. Different examples for monitoring geomorphology as a crucial discipline of geodiversity using RS are provided, discussing the implementation of RS technologies such as LiDAR, RADAR, as well as multi-spectral and hyperspectral sensor technologies. Furthermore, data products and RS technologies that could be used in the future for monitoring geomorphology are introduced. The use of spectral traits (ST) and spectral trait variation (STV) approaches with RS enable the status, changes, and disturbances of geomorphic diversity to be monitored. We focus on the requirements for future geomorphology monitoring specifically aimed at overcoming some key limitations of ecological modeling, namely: the implementation and linking of in-situ, close-range, air- and spaceborne RS technologies, geomorphic traits, and data science approaches as crucial components for a better understanding of the geomorphic impacts on complex ecosystems. This paper aims to impart multidimensional geomorphic information obtained by RS for improved utilization in biodiversity monitoring.

Endosomal sorting complexes required for transport (ESCRT) drive cell surface receptor degradation resulting in attenuation of oncogenic signaling and pointing to a tumor suppressor function. Here, we show that loss of function of an ESCRT protein (HD-PTP encoded by the PTPN23 gene, located on the tumor suppressor gene cluster 3p21.3) drives tumorigenesis in vivo. Indeed, Ptpn23+/− loss predisposes mice to sporadic lung adenoma, B cell lymphoma, and promotes Myc-driven lymphoma onset, dissemination, and aggressiveness. Ptpn23+/−-derived tumors exhibit an unaltered remaining allele and maintain 50% of HD-PTP expression. Consistent with the role of HD-PTP in attenuation of integrin recycling, cell migration, and invasion, hemizygous Ptpn23+/− loss increases integrin β1-dependent B cell lymphoma survival and dissemination. Finally, we reveal frequent PTPN23 deletion and downregulation in human tumors that correlates with poor survival. Altogether, we establish HD-PTP/PTPN23 as a prominent haploinsufficient tumor suppressor gene preventing tumor progression through control of integrin trafficking.

libRadtran is a widely used software package for radiative transfer calculations. It allows one to compute (polarized) radiances, irradiance, and actinic fluxes in the solar and thermal spectral regions. libRadtran has been used for various applications, including remote sensing of clouds, aerosols and trace gases in the Earth's atmosphere, climate studies, e.g., for the calculation of radiative forcing due to different atmospheric components, for UV forecasting, the calculation of photolysis frequencies, and for remote sensing of other planets in our solar system. The package has been described in Mayer and Kylling (2005). Since then several new features have been included, for example polarization, Raman scattering, a new molecular gas absorption parameterization, and several new parameterizations of cloud and aerosol optical properties. Furthermore, a graphical user interface is now available, which greatly simplifies the usage of the model, especially for new users. This paper gives an overview of libRadtran version 2.0.1 with a focus on new features. Applications including these new features are provided as examples of use. A complete description of libRadtran and all its input options is given in the user manual included in the libRadtran software package, which is freely available at http://www.libradtran.org.

Membrane trafficking of integrins plays a pivotal role in cell proliferation and migration. How endocytosed integrins are targeted either for recycling or lysosomal delivery is not fully understood. Here, we show that fibronectin (FN) binding to α5β1 integrin triggers ubiquitination and internalization of the receptor complex. Acidification facilitates FN dissociation from integrin α5β1 in vitro and in early endosomes, promoting receptor complex deubiquitination by the USP9x and recycling to the cell surface. Depending on residual ligand occupancy of receptors, some α5β1 integrins remain ubiquitinated and are captured by ESCRT-0/I, containing histidine domain-containing protein tyrosine phosphatase (HD-PTP) and ubiquitin-associated protein 1 (UBAP1), and are directed for lysosomal proteolysis, limiting receptor downstream signaling and cell migration. Thus, HD-PTP or UBAP1 depletion confers a pro-invasive phenotype. Thus, pH-dependent FN-integrin dissociation and deubiquitination of the activated integrin α5β1 are required for receptor resensitization and cell migration, representing potential targets to modulate tumor invasiveness.

Environmental remote sensing has faced increasing satellite data availability, advanced algorithms for thematic analysis, and novel concepts of ground truth. For that reason, contents and concepts of learning and teaching remote sensing are constantly evolving. This eventually leads to the intuition of methodologically linking academic learning assignments with case-related scopes of application. In order to render case-related learning possible, smart teaching and interactive learning contexts are appreciated and required for remote sensing. That is due to the fact that those contexts are considered promising to trigger and gradually foster students’ comprehensive interdisciplinary thinking. To this end, the following contribution introduces the case-related concept of applying simulation games as a promising didactic format in teaching/learning assignments of remote sensing. As to methodology, participating students have been invited to take on individual roles bound to technology-related profiles (e.g., satellite-mission planning, irrigation, etc.) Based on the scenario, stakeholder teams have been requested to elaborate, analyze and negotiate viable solutions for soil moisture monitoring in a defined context. Collaboration has been encouraged by providing the protected, specifically designed remoSSoil-incubator environment. This letter-type paper aims to introduce the simulation game technique in the context of remote sensing as a type of scholarly teaching; it evaluates learning outcomes by adopting certain techniques of scholarship of teaching and learning (SoTL); and it provides food for thought of replicating, adapting and enhancing simulation games as an innovative, disruptive next-generation learning environment in remote sensing.

Surface soil moisture (SSM) plays a critical role in many hydrological, biological and biogeochemical processes. It is relevant to farmers, scientists, and policymakers for making effective land management decisions. However, coarse spatial resolution and complex interactions of microwave radiation with surface roughness and vegetation structure present limitations within active remote sensing products to directly monitor soil moisture variations with sufficient detail. This paper discusses a strategy to use vegetation indices (VI) such as greenness, water stress, coverage, vigor, and growth dynamics, derived from Earth Observation (EO) data for an indirect characterization of SSM conditions. In this regional-scale study of a wetland environment, correlations between the coarse Advanced SCATterometer-Soil Water Index (ASCAT-SWI or SWI) product and statistical measurements of four vegetation indices from higher resolution Sentinel-2 data were analyzed. The results indicate that the mean value of Fraction of Absorbed Photosynthetically Active Radiation (FAPAR) correlates most strongly to the SWI and that the wet season vegetation traits show stronger linear relation to the SWI than during the dry season. The correlation between VIs and SWI was found to be independent of the underlying dominant vegetation classes which are not derived in real-time. Therefore, fine-scale vegetation information from optical satellite data convey the spatial heterogeneity missed by coarse synthetic aperture radar (SAR)-derived SSM products and is linked to the SSM condition underneath for regionalization purposes.

The article analyses the composition of colour in the mise-en-scène of the zombie-movies REC, 28 Days Later and World War Z via a computer based approach. It first evaluates some of the methodological problems of common colour-quantisation by using clustering-algorithms in the context of film studies, then a new developed process is presented which builds on the theory of colour contrasts by Johannes Itten. A simple statistical analysis of two contrast ratios for each of the movies demonstrates that this approach is capable of providing detailed insights into the composition of colour in movies in general. Furthermore, the analysis of the three movies reveals that the accentuation of colour contrast relations serves different functions: colours can support the narrative structure of the movie, emphasize repeating motifs or establish an autonomous aesthetic space.

Abstract Activation of AMPK has been associated with pro‐atrophic signaling in muscle. However, AMPK also has anti‐inflammatory effects, suggesting that in cachexia, a syndrome of inflammatory‐driven muscle wasting, AMPK activation could be beneficial. Here we show that the AMPK agonist AICAR suppresses IFNγ/TNFα‐induced atrophy, while the mitochondrial inhibitor metformin does not. IFNγ/TNFα impair mitochondrial oxidative respiration in myotubes and promote a metabolic shift to aerobic glycolysis, similarly to metformin. In contrast, AICAR partially restored metabolic function. The effects of AICAR were prevented by the AMPK inhibitor Compound C and were reproduced with A‐769662, a specific AMPK activator. AICAR and A‐769662 co‐treatment was found to be synergistic, suggesting that the anti‐cachectic effects of these drugs are mediated through AMPK activation. AICAR spared muscle mass in mouse models of cancer and LPS induced atrophy. Together, our findings suggest a dual function for AMPK during inflammation‐driven atrophy, wherein it can play a protective role when activated exogenously early in disease progression, but may contribute to anabolic suppression and atrophy when activated later through mitochondrial dysfunction and subsequent metabolic stress.

In this paper we aim to show a proof-of-principle approach to detect and monitor weed management using glyphosate-based herbicides in agricultural practices. In a case study in Germany, we demonstrate the application of Sentinel-2 multispectral time-series data. Spectral broadband vegetation indices were analysed to observe vegetation traits and weed damage arising from herbicide-based management. The approach has been validated with stakeholder information about herbicide treatment using commercial products. As a result, broadband NDVI calculated from Sentinel-2 data showed explicit feedback after the glyphosate-based herbicide treatment. Vegetation damage could be detected after just two days following of glyphosate-based herbicide treatment. This trend was observed in three different application scenarios, i.e., during growing stage, before harvest and after harvest. The findings of the study demonstrate the feasibility of satellite based broadband NDVI data for the detection of glyphosate-based herbicide treatment and, e.g., the monitoring of latency to harvesting. The presented results can be used to implement monitoring concepts to provide the necessary transparency about weed treatment in agricultural practices and to support environmental monitoring.

In the face of rapid global change it is imperative to preserve geodiversity for the overall conservation of biodiversity. Geodiversity is important for understanding complex biogeochemical and physical processes and is directly and indirectly linked to biodiversity on all scales of ecosystem organization. Despite the great importance of geodiversity, there is a lack of suitable monitoring methods. Compared to conventional in-situ techniques, remote sensing (RS) techniques provide a pathway towards cost-effective, increasingly more available, comprehensive, and repeatable, as well as standardized monitoring of continuous geodiversity on the local to global scale. This paper gives an overview of the state-of-the-art approaches for monitoring soil characteristics and soil moisture with unmanned aerial vehicles (UAV) and air- and spaceborne remote sensing techniques. Initially, the definitions for geodiversity along with its five essential characteristics are provided, with an explanation for the latter. Then, the approaches of spectral traits (ST) and spectral trait variations (STV) to record geodiversity using RS are defined. LiDAR (light detection and ranging), thermal and microwave sensors, multispectral, and hyperspectral RS technologies to monitor soil characteristics and soil moisture are also presented. Furthermore, the paper discusses current and future satellite-borne sensors and missions as well as existing data products. Due to the prospects and limitations of the characteristics of different RS sensors, only specific geotraits and geodiversity characteristics can be recorded. The paper provides an overview of those geotraits.

Isocitrate Dehydrogenase-1 (IDH1) is a driver gene in several cancers including brain tumors such as low-grade and high-grade gliomas. Mutations of SMARCB1 were described in atypical teratoid rhabdoid tumors and to date have not been associated with the pathogenesis of medulloblastoma. We report concurrent IDH1 and SMARCB1 mutations in a medulloblastoma patient. We searched the catalog of somatic mutations in cancer (COSMIC) database and other mutation databases and -to our knowledge- this is the first reported case of medulloblastoma harboring both mutations together. Our patient is a 13-year-old male presenting with headache and vomiting at diagnosis. MRI revealed left cerebellar expansive lesion with no evidence of metastasis. A histopathological diagnosis of desmoplastic/nodular medulloblastoma was made after complete resection of the tumor. Immunophenotypic characterization and methylation profiling suggested a medulloblastoma with SHH activation. Next generation sequencing of a panel of 400 genes revealed heterozygous somatic IDH1(p.R132C), SMARCB1(p.R201Q), and CDH11(p.L625T) mutations. The patient was treated according to the HIT-SIOP PNET 4 protocol. He is in complete remission more than 2 years after diagnosis. In conclusion, increasing use of high throughput sequencing will certainly increase the frequency with which rare mutations or mutation combinations are identified. The exact frequency of this mutation combination and whether it has any particular therapeutic implications or prognostic relevance requires further investigation.

The ruminal degradability of dry matter (DM) and neutral detergent fiber (NDF) of 9 sugarcane varieties ensiled 15 months after planting was evaluated, using 3 fistulated Holstein x Zebu cows and incubation periods of 0, 6, 12, 24, 72 and 96 h in a randomized complete block design. Dry matter, crude protein (CP), mineral matter (MM), NDF, pH and in-situ degradability levels were determined. There were significant differences in composition of all evaluated parameters in the silages, except for CP, with the following variations: DM (19.7–23.2%), CP (2.70–3.47%), MM (3.2–5.2%), NDF (67.6–73.8%) and pH (3.8–4.2). The DM fraction ‘a’ differed among sugarcane varieties, with SP 801816 presenting the highest soluble fraction (26.83%). Effective degradability (ED) of DM (32.7–40.9%) and degradation rate ‘c’ did not differ among varieties. The ED of NDF and fraction ‘a’ did not differ among silages, but there were significant differences in fraction ‘b’, with a variation from 36.4 to 41.2%. Highest NDF ED occurred for the varieties RB 835486 (22%) and SP 791011 (21.1%). Further studies with these two varieties with the addition of inoculants and additives at ensiling are needed along with feeding studies to determine animal performance data.

Aromatherapy claims that citrus essential oils exert mood lifting effects. Controlled studies, however, have yielded inconsistent results. Notably, studies so far did not control for odor pleasantness, although pleasantness is a critical determinant of emotional responses to odors. This study investigates mood lifting effects of d-(+)-limonene, the most prominent substance in citrus essential oils, with respect to odor quality judgments.Negative mood was induced within 78 participants using a helplessness paradigm (unsolvable social discrimination task). During this task, participants were continuously (mean duration: 19.5 min) exposed to d-(+)-limonene (n = 25), vanillin (n = 26), or diethyl phthalate (n = 27). Participants described their mood (Self-Assessment-Manikin, basic emotion ratings) and judged the odors’ quality (intensity, pleasantness, unpleasantness, familiarity) prior to and following the helplessness induction. The participants were in a less positive mood after the helplessness induction (p < .001), irrespective of the odor condition. Still, the more pleasant the participants judged the odors, the less effective the helplessness induction was in reducing happiness (p = .019).The results show no odor specific mood lifting effect of d-(+)-limonene, but indicate a positive effect of odor pleasantness on mood. The study highlights the necessity to evaluate odor judgments in aromatherapy research.

QUESTIONS UNDER STUDY: Completeness is important in cancer registration. Identifying areas to improve registry procedures might help to maximise completeness. We examined characteristics of childhood cancer cases that were registered via death certificate notification (DCN) rather than during life, and estimated completeness of the Swiss Childhood Cancer Registry (SCCR). METHODS: We analysed data from all children who died from cancer in Switzerland between 1985–2009 at age

Mechanisms of adaptation to environmental changes in osmolarity are fundamental for cellular and organismal survival. Here we identify a novel osmotic stress resistance pathway in Caenorhabditis elegans (C. elegans), which is dependent on the metabolic master regulator 5'-AMP-activated protein kinase (AMPK) and its negative regulator Folliculin (FLCN). FLCN-1 is the nematode ortholog of the tumor suppressor FLCN, responsible for the Birt-Hogg-Dubé (BHD) tumor syndrome. We show that flcn-1 mutants exhibit increased resistance to hyperosmotic stress via constitutive AMPK-dependent accumulation of glycogen reserves. Upon hyperosmotic stress exposure, glycogen stores are rapidly degraded, leading to a significant accumulation of the organic osmolyte glycerol through transcriptional upregulation of glycerol-3-phosphate dehydrogenase enzymes (gpdh-1 and gpdh-2). Importantly, the hyperosmotic stress resistance in flcn-1 mutant and wild-type animals is strongly suppressed by loss of AMPK, glycogen synthase, glycogen phosphorylase, or simultaneous loss of gpdh-1 and gpdh-2 enzymes. Our studies show for the first time that animals normally exhibit AMPK-dependent glycogen stores, which can be utilized for rapid adaptation to either energy stress or hyperosmotic stress. Importantly, we show that glycogen accumulates in kidneys from mice lacking FLCN and in renal tumors from a BHD patient. Our findings suggest a dual role for glycogen, acting as a reservoir for energy supply and osmolyte production, and both processes might be supporting tumorigenesis.

Forest ecosystems fulfill a whole host of ecosystem functions that are essential for life on our planet. However, an unprecedented level of anthropogenic influences is reducing the resilience and stability of our forest ecosystems as well as their ecosystem functions. The relationships between drivers, stress, and ecosystem functions in forest ecosystems are complex, multi-faceted, and often non-linear, and yet forest managers, decision makers, and politicians need to be able to make rapid decisions that are data-driven and based on short and long-term monitoring information, complex modeling, and analysis approaches. A huge number of long-standing and standardized forest health inventory approaches already exist, and are increasingly integrating remote-sensing based monitoring approaches. Unfortunately, these approaches in monitoring, data storage, analysis, prognosis, and assessment still do not satisfy the future requirements of information and digital knowledge processing of the 21st century. Therefore, this paper discusses and presents in detail five sets of requirements, including their relevance, necessity, and the possible solutions that would be necessary for establishing a feasible multi-source forest health monitoring network for the 21st century. Namely, these requirements are: (1) understanding the effects of multiple stressors on forest health; (2) using remote sensing (RS) approaches to monitor forest health; (3) coupling different monitoring approaches; (4) using data science as a bridge between complex and multidimensional big forest health (FH) data; and (5) a future multi-source forest health monitoring network. It became apparent that no existing monitoring approach, technique, model, or platform is sufficient on its own to monitor, model, forecast, or assess forest health and its resilience. In order to advance the development of a multi-source forest health monitoring network, we argue that in order to gain a better understanding of forest health in our complex world, it would be conducive to implement the concepts of data science with the components: (i) digitalization; (ii) standardization with metadata management after the FAIR (Findability, Accessibility, Interoperability, and Reusability) principles; (iii) Semantic Web; (iv) proof, trust, and uncertainties; (v) tools for data science analysis; and (vi) easy tools for scientists, data managers, and stakeholders for decision-making support.

TOR (target of rapamycin), an evolutionarily-conserved serine/threonine kinase, acts as a central regulator of cell growth, proliferation and survival in response to nutritional status, growth factor, and stress signals. It plays a crucial role in coordinating the balance between cell growth and cell death, depending on cellular conditions and needs. As such, TOR has been identified as a key modulator of autophagy for more than a decade, and several deregulations of this pathway have been implicated in a variety of pathological disorders, including cancer. At the molecular level, autophagy regulates several survival or death signaling pathways that may decide the fate of cancer cells; however, the relationship between autophagy pathways and cancer are still nascent. In this review, we discuss the recent cellular signaling pathways regulated by TOR, their interconnections to autophagy, and the clinical implications of TOR inhibitors in cancer.