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Climate change increases the occurrence and severity of droughts due to increasing temperatures, altered circulation patterns, and reduced snow occurrence. While Europe has suffered from drought events in the last decade unlike ever seen since the beginning of weather recordings, harmonized long-term datasets across the continent are needed to monitor change and support predictions. Here we present soil moisture data from 66 cosmic-ray neutron sensors (CRNSs) in Europe (COSMOS-Europe for short) covering recent drought events. The CRNS sites are distributed across Europe and cover all major land use types and climate zones in Europe. The raw neutron count data from the CRNS stations were provided by 24 research institutions and processed using state-of-the-art methods. The harmonized processing included correction of the raw neutron counts and a harmonized methodology for the conversion into soil moisture based on available in situ information. In addition, the uncertainty estimate is provided with the dataset, information that is particularly useful for remote sensing and modeling applications. This paper presents the current spatiotemporal coverage of CRNS stations in Europe and describes the protocols for data processing from raw measurements to consistent soil moisture products. The data of the presented COSMOS-Europe network open up a manifold of potential applications for environmental research, such as remote sensing data validation, trend analysis, or model assimilation. The dataset could be of particular importance for the analysis of extreme climatic events at the continental scale. Due its timely relevance in the scope of climate change in the recent years, we demonstrate this potential application with a brief analysis on the spatiotemporal soil moisture variability. The dataset, entitled “Dataset of COSMOS-Europe: A European network of Cosmic-Ray Neutron Soil Moisture Sensors”, is shared via Forschungszentrum Jülich: https://doi.org/10.34731/x9s3-kr48 (Bogena and Ney, 2021).

An improved management of secondary raw materials (SRM) is a crucial contribution for a circular economy and necessitates knowledge about the composition of wastes and SRM. However, this information is scarce and has to be determined with chemical analysis (CA). CA of SRM faces challenges, which can be approached by using round robin tests (RRT) to identify deviations from the “true value” of an element/molecule content. An RRT is a testing approach, which involves multiple labs to analyze one or more samples and evaluates the lab results with regard to the goal of the RRT. This article presents a systematic literature review and investigates which purposes and which performance parameters (PP) are commonly applied in RRT of SRM. The examined literature shows that the two main purposes applied are assessment of method performance and assessment of lab performance. PP can be categorized into trueness performance parameters (TPP; assessing the deviation of a value from a reference value) and precision performance parameters (PPP; describing the variability of a data set). The main TPP identified are z score and relative deviation, the main PPP identified are standard deviation and relative standard deviation. These results offer the conclusions that RRT can be used as a bespoke method to deal with analytical effects and that the selection of PP for an RRT could be based on simplicity.

Abstract Neuropsychological studies reported that shift workers show reduced cognitive performance and circadian dysfunctions which may impact structural and functional brain networks. Here we tested the hypothesis whether night shift work is associated with resting-state functional connectivity (RSFC), cortical thickness and gray matter volume in participants of the 1000BRAINS study for whom information on night shift work and imaging data were available. 13 PRESENT and 89 FORMER night shift workers as well as 430 control participants who had never worked in shift (NEVER) met these criteria and were included in our study. No associations between night shift work, three graph-theoretical measures of RSFC of 7 functional brain networks and brain morphology were found after multiple comparison correction. Preceding multiple comparison correction, our results hinted at an association between more years of shift work and higher segregation of the visual network in PRESENT shift workers and between shift work experience and lower gray matter volume of the left thalamus. Extensive neuropsychological investigations supplementing objective imaging methodology did not reveal an association between night shift work and cognition after multiple comparison correction. Our pilot study suggests that night shift work does not elicit general alterations in brain networks and affects the brain only to a limited extent. These results now need to be corroborated in studies with larger numbers of participants.

In this editorial, we sketch the intellectual agenda for a themed issue on German Theory. We understand German Theory as a creative and dialogical space to engage a multitude of thought styles, common in the Geisteswissenschaften and to bring them into conversations with anglophone, as much as francophone, lusophone, Italian, Spanish and other forms of Theory. This agenda promotes a ‚provincialization‘ of anglophone Geography that is connecting these thought styles rather than confining them to bounded provinces in debate. „German Theory“, thus understood, is ultimately an entangled theory.

Cachexia is associated with poor prognosis in heart failure. Here the authors show that mice and patients with cardiac cachexia display reduced skeletal muscle expression and circulating levels of Musclin. Musclin ablation in skeletal muscle worsens, while its muscle-specific overexpression ameliorates heart failure in mice.

Introduction: Dissecting the intricate networks of covalent and non-covalent interactions that stabilize complex protein structures is notoriously difficult and requires subtle atomic-level exchanges to precisely affect local chemical functionality. The function of the Orange Carotenoid Protein (OCP), a light-driven photoswitch involved in cyanobacterial photoprotection, depends strongly on two H-bonds between the 4-ketolated xanthophyll cofactor and two highly conserved residues in the C-terminal domain (Trp288 and Tyr201).Method: By orthogonal translation, we replaced Trp288 in Synechocystis OCP with 3-benzothienyl-L-alanine (BTA), thereby exchanging the imino nitrogen for a sulphur atom.Results: Although the high-resolution (1.8 Å) crystal structure of the fully photoactive OCP-W288_BTA protein showed perfect isomorphism to the native structure, the spectroscopic and kinetic properties changed distinctly. We accurately parameterized the effects of the absence of a single H-bond on the spectroscopic and thermodynamic properties of OCP photoconversion and reveal general principles underlying the design of photoreceptors by natural evolution.Discussion: Such “molecular surgery” is superior over trial-and-error methods in hypothesis-driven research of complex chemical systems.

To reveal impacts of sexual mode on genome content, we compared chromosome-scale assemblies of the outcrossing nematode Caenorhabditis nigoni to its self-fertile sibling species, C. briggsaeC. nigoni's genome resembles that of outcrossing relatives but encodes 31% more protein-coding genes than C. briggsaeC. nigoni genes lacking C. briggsae orthologs were disproportionately small and male-biased in expression. These include the male secreted short (mss) gene family, which encodes sperm surface glycoproteins conserved only in outcrossing species. Sperm from mss-null males of outcrossing C. remanei failed to compete with wild-type sperm, despite normal fertility in noncompetitive mating. Restoring mss to C. briggsae males was sufficient to enhance sperm competitiveness. Thus, sex has a pervasive influence on genome content that can be used to identify sperm competition factors.

Collaboration among scientists has a major influence on scientific progress. Such collaboration often results from scientific meetings, where scientists gather to present and discuss their research and to meet potential collaborators. However, most scientific meetings have inherent biases, such as the availability of research funding or the selection bias of professional societies that make it difficult to study the effect of the meeting per se on scientific productivity. To evaluate the effects of scientific meetings on collaboration and progress independent of these biases, we conducted a study of the annual symposia held by the International Milk Genomics Consortium (IMGC) over a 12-year period. In our study, we conducted permutation testing to analyze the effectiveness of the IMGC in facilitating collaboration and productivity in a community of milk scientists who were meeting attendees relative to non-attendees. Using the number of co-authorships on published papers as a measure of collaboration, our analysis revealed that scientists who attended the symposium were associated with more collaboration than were scientists who did not attend. Furthermore, we evaluated the scientific progress of consortium attendees by analyzing publication rate and article impact. We found that IMGC attendees, in addition to being more collaborative, were also more productive and influential than were non-attendees who published in the same field. The results of our study suggest that the annual symposium encouraged interactions among disparate scientists and increased research productivity, exemplifying the positive effect of scientific meetings on both collaboration and progress.

Abstract Background Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BC). Treatment options for TNBC patients are limited and further insights into disease aetiology are needed to develop better therapeutic approaches. microRNAs’ ability to regulate multiple targets could hold a promising discovery approach to pathways relevant for TNBC aggressiveness. Thus, we address the role of miRNAs in controlling three signalling pathways relevant to the biology of TNBC, and their downstream phenotypes. Methods To identify miRNAs regulating WNT/β-catenin, c-Met, and integrin signalling pathways, we performed a high-throughput targeted proteomic approach, investigating the effect of 800 miRNAs on the expression of 62 proteins in the MDA-MB-231 TNBC cell line. We then developed a novel network analysis, Pathway Coregulatory (PC) score, to detect miRNAs regulating these three pathways. Using in vitro assays for cell growth, migration, apoptosis, and stem-cell content, we validated the function of candidate miRNAs. Bioinformatic analyses using BC patients’ datasets were employed to assess expression of miRNAs as well as their pathological relevance in TNBC patients. Results We identified six candidate miRNAs coordinately regulating the three signalling pathways. Quantifying cell growth of three TNBC cell lines upon miRNA gain-of-function experiments, we characterised miR-193b as a strong and consistent repressor of proliferation. Importantly, the effects of miR-193b were stronger than chemical inhibition of the individual pathways. We further demonstrated that miR-193b induced apoptosis, repressed migration, and regulated stem-cell markers in MDA-MB-231 cells. Furthermore, miR-193b expression was the lowest in patients classified as TNBC or Basal compared to other subtypes. Gene Set Enrichment Analysis showed that miR-193b expression was significantly associated with reduced activity of WNT/β-catenin and c-Met signalling pathways in TNBC patients. Conclusions Integrating miRNA-mediated effects and protein functions on networks, we show that miRNAs predominantly act in a coordinated fashion to activate or repress connected signalling pathways responsible for metastatic traits in TNBC. We further demonstrate that our top candidate, miR-193b, regulates these phenotypes to an extent stronger than individual pathway inhibition, thus emphasizing that its effect on TNBC aggressiveness is mediated by the coordinated repression of these functionally interconnected pathways.

Abstract The evolution of evidence and availability of Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines have enabled assessment of pharmacogenetic (PGx) actionability and clinical implementation. However, population‐level actionability is not well‐characterized. We leveraged the Alabama Genomic Health Initiative (AGHI) to evaluate population‐level PGx actionability. Participants (>18 years), representing all 67 Alabama counties, were genotyped using the Illumina Global Screening array. Using CPIC guidelines, actionability was evaluated using (1) genotype data and genetic ancestry, (2) prescribing data, and (3) combined genotype and medication data. Of 6,331 participants, 4230 had genotype data and 3386 had genotype and prescription data (76% women; 76% White/18% Black [self‐reported]). Genetic ancestry was concordant with self‐reported race. For CPIC level A genes, 98.6% had an actionable genotype (99.4% Blacks/African; 98.5% White/European). With the exception of DPYD and CYP2C19, the prevalence of actionable genotypes by gene differed significantly by race. Based on prescribing, actionability was highest for CYP2D6 (70.9%), G6PD (54.1%), CYP2C19 (53.5%), and CYP2C9 (47.5%). Among participants prescribed atenolol, carvedilol, or metoprolol, ~ 50% had an actionable ADRB1 genotype, associated with decreased therapeutic response, with higher actionability among Blacks compared to Whites (62.5% vs. 47.4%; p

Abstract This study investigates whether a chronotherapeutic treatment of hepatocellular carcinoma (HCC) may improve treatment efficacy and mitigate side effects on non‐tumoral liver (NTL). HCC was induced in Per2::luc mice which were irradiated at four time points of the day. Proliferation and DNA‐double strand breaks were analyzed in irradiated and nonirradiated animals by detection of Ki67 and γ‐H2AX. Prior to whole animal experiments, organotypic slice cultures were investigated to determine the dosage to be used in whole animal experiments. Irradiation was most effective at the proliferation peaks in HCC at ZT02 (early inactivity phase) and ZT20 (late activity phase). Irradiation effects on NTL were minimal at ZT20. As compared with NTL, nonirradiated HCC revealed disruption in daily variation and downregulation of all investigated clock genes except Per1. Irradiation affected rhythmic clock gene expression in NTL and HCC at all ZTs except at ZT20 (late activity phase). Irradiation at ZT20 had no effect on total leukocyte numbers. Our results indicate ZT20 as the optimal time point for irradiation of HCC in mice at which the ratio between efficacy of tumor treatment and toxic side effects was maximal. Translational studies are now needed to evaluate whether the late activity phase is the optimal time point for irradiation of HCC in man.

Trisomy and triploidy, defined as the presence of a third copy of one or all chromosomes, respectively, are deleterious in many species including humans. Previous studies have demonstrated that Caenorhabditis elegans with a third copy of the X chromosome are viable and fertile. However, the extra X chromosome was shown to preferentially segregate into the first polar body during oocyte meiosis to produce a higher frequency of euploid offspring than would be generated by random segregation. Here, we demonstrate that extra autosomes are preferentially eliminated by triploid C. elegans and trisomy IV C. elegans Live imaging of anaphase-lagging chromosomes and analysis of REC-8 staining of metaphase II spindles revealed that, in triploids, some univalent chromosomes do not lose cohesion and preferentially segregate intact into the first polar body during anaphase I, whereas other autosomes segregate chromatids equationally at anaphase I and eliminate some of the resulting single chromatids during anaphase II. We also demonstrate asymmetry in the anaphase spindle, which may contribute to the asymmetric segregation. This study reveals a pathway that allows aneuploid parents to produce euploid offspring at higher than random frequency.

Lettuce (Lactuca sativa) is a major crop and a member of the large, highly successful Compositae family of flowering plants. Here we present a reference assembly for the species and family. This was generated using whole-genome shotgun Illumina reads plus in vitro proximity ligation data to create large superscaffolds; it was validated genetically and superscaffolds were oriented in genetic bins ordered along nine chromosomal pseudomolecules. We identify several genomic features that may have contributed to the success of the family, including genes encoding Cycloidea-like transcription factors, kinases, enzymes involved in rubber biosynthesis and disease resistance proteins that are expanded in the genome. We characterize 21 novel microRNAs, one of which may trigger phasiRNAs from numerous kinase transcripts. We provide evidence for a whole-genome triplication event specific but basal to the Compositae. We detect 26% of the genome in triplicated regions containing 30% of all genes that are enriched for regulatory sequences and depleted for genes involved in defence.

Early embryonic stages of pluripotency are modeled for epigenomic studies primarily with human embryonic stem cells (ESC) or induced pluripotent stem cells (iPSCs). For analysis of DNA methylation however, ESCs and iPSCs do not accurately reflect the DNA methylation levels found in preimplantation embryos. Whole genome bisulfite sequencing (WGBS) approaches have revealed the presence of large partially methylated domains (PMDs) covering 30%-40% of the genome in oocytes, preimplantation embryos, and placenta. In contrast, ESCs and iPSCs show abnormally high levels of DNA methylation compared to inner cell mass (ICM) or placenta. Here we show that dental pulp stem cells (DPSCs), derived from baby teeth and cultured in serum-containing media, have PMDs and mimic the ICM and placental methylome more closely than iPSCs and ESCs. By principal component analysis, DPSC methylation patterns were more similar to two other neural stem cell types of human derivation (EPI-NCSC and LUHMES) and placenta than were iPSCs, ESCs or other human cell lines (SH-SY5Y, B lymphoblast, IMR90). To test the suitability of DPSCs in modeling epigenetic differences associated with disease, we compared methylation patterns of DPSCs derived from children with chromosome 15q11.2-q13.3 maternal duplication (Dup15q) to controls. Differential methylation region (DMR) analyses revealed the expected Dup15q hypermethylation at the imprinting control region, as well as hypomethylation over SNORD116, and novel DMRs over 147 genes, including several autism candidate genes. Together these data suggest that DPSCs are a useful model for epigenomic and functional studies of human neurodevelopmental disorders. Stem Cells 2017;35:981-988.

OBJECTIVES/GOALS: Supported by the State of Alabama, the Alabama Genomic Health Initiative (AGHI) is aimed at preventing and treating common conditions with a genetic basis. This joint UAB Medicine-HudsonAlpha Institute for Biotechnology effort provides genomic testing, interpretation, and counseling free of charge to residents in each of Alabama’s 67 counties. METHODS/STUDY POPULATION: Launched in 2017, as a state-wide population cohort, AGHI (1.0) enrolled 6,331 Alabamians and returned individual risk of disease(s) related to the ACMG SF v2.0 medically actionable genes. In 2021, the cohort was expanded to include a primary care cohort. AGHI (2.0) has enrolled 750 primary care patients, returning individual risk of disease(s) related to the ACMG SF v3.1 gene list and pre-emptive pharmacogenetics (PGx) to guide medication therapy. Genotyping is done on the Illumina Global Diversity Array with Sanger sequencing to confirm likely pathogenic / pathogenic variants in medically actionable genes and CYP2D6 copy number variants using Taqman assays, resulting in a CLIA-grade report. Disease risk results are returned by genetic counselors and Pharmacogenetics results are returned by Pharmacists. RESULTS/ANTICIPATED RESULTS: We have engaged a statewide community (>7000 participants), returning 94 disease risk genetic reports and 500 PGx reports. Disease risk reports include increased predisposition to cancers (n=38), cardiac diseases (n=33), metabolic (n=12), other (n=11). 100% of participants harbor an actionable PGx variant, 70% are on medication with PGx guidance, 48% harbor PGx variants and are taking medications affected. In 10% of participants, pharmacists sent an active alert to the provider to consider/ recommend alternative medication. Most commonly impacted medications included antidepressants, NSAIDS, proton-pump inhibitors and tramadol. To enable the EMR integration of genomic information, we have developed an automated transfer of reports into the EMR with Genetics Reports and PGx reports viewable in Cerner. DISCUSSION/SIGNIFICANCE: We share our experience on pre-emptive implementation of genetic risk and pharmacogenetic actionability at a population and clinic level. Both patients and providers are actively engaged, providing feedback to refine the return of results. Real time alerts with guidance at the time of prescription are needed to ensure future actionability and value.

Substantial quantities of solid livestock waste are potential sources of nutrients for agroecological production on small-scale farms. However, processes used to manage and dispose of this type of waste must be able to eliminate pathogenic microorganisms. This work aimed to evaluate composting and vermicomposting processes by inoculating efficient microorganisms (EMs) at the field level. Composting and vermicomposting were performed with a mixture of cattle and goat manure and sawdust (2:1:1), with the inoculation of EMs at concentrations of 0, 2, and 4 mL L-1. In vermicomposting experiments, Lumbricus rubellus (100 g 250 dm-3 substrate) were inoculated. After the maturation and stabilization phases of the compost, concentrations of organic carbon, macronutrients, micronutrients, heavy metals, thermotolerant coliforms, and Salmonella spp. were analyzed. The composting experiments, regardless of the presence of EMs, have been shown to have higher humidity. Also, the final compost had a lower pH value. Macronutrients, such as P, K, Ca, and S, were observed to a greater extent in the composting experiments associated with 4 mL of EMs (EM4); while organic carbon and Mg were higher in vermicomposting. The vermicomposting process also allowed for more effective elimination of pathogens, such as thermotolerant coliforms, especially when associated with 2 mL of EMs (EM2). The compost products produced allowed waste with potential agroecological use to be recognized as important.

In this editorial, we introduce the special section on the politics of memory of „Kiel 1969“, the famous German geographers' conference, during which, as the myth narrates, a revolution took place within the discipline of German-language geography. By introducing and contextualizing the three individual statements by Julia Verne, Ulf Strohmayer and Peter Weichhart, who all recount their entanglements with the myth of „Kiel 1969“, we invite the reader to reflect upon the dynamics through which „events“ turn into „myths“ that shape individual careers and strategic struggles within the discipline.

Integrated management of municipal solid waste seeks sustainability under the premises of environmental protection, health promotion, and economic development. In this context, this article proposes actions and policy tools for local governments to improve quality and governance in waste management. A set of 23 actions is proposed based on existing conceptual models and available legislation. The results are presented in three levels as follows: planning of the administrative and operational structure, waste management, and performance evaluation. The results showed that the proposed actions need to be implemented through policy tools, such as municipal legislation, social communication, normative instructions, and technical studies. The applicability of the proposed methodology, which might be replicated in any municipality to increase the efficiency of the waste management system, was positively evaluated in a medium-sized Brazilian city, which presented an overall attendance level of 52%.

Mirror-image proteins, composed of d-amino acids, are an attractive therapeutic modality, as they exhibit high metabolic stability and lack immunogenicity. Development of mirror-image binding proteins is achieved through chemical synthesis of d-target proteins, phage display library selection of l-binders and chemical synthesis of (mirror-image) d-binders that consequently bind the physiological l-targets. Monobodies are well-established synthetic (l-)binding proteins and their small size (~90 residues) and lack of endogenous cysteine residues make them particularly accessible to chemical synthesis. Here, we develop monobodies with nanomolar binding affinities against the d-SH2 domain of the leukemic tyrosine kinase BCR::ABL1. Two crystal structures of heterochiral monobody-SH2 complexes reveal targeting of the pY binding pocket by an unconventional binding mode. We then prepare potent d-monobodies by either ligating two chemically synthesized d-peptides or by self-assembly without ligation. Their proper folding and stability are determined and high-affinity binding to the l-target is shown. d-monobodies are protease-resistant, show long-term plasma stability, inhibit BCR::ABL1 kinase activity and bind BCR::ABL1 in cell lysates and permeabilized cells. Hence, we demonstrate that functional d-monobodies can be developed readily. Our work represents an important step towards possible future therapeutic use of d-monobodies when combined with emerging methods to enable cytoplasmic delivery of monobodies. In this work, the authors develop mirror-image monobodies (Mb) made of D-amino acids against the BCR::ABL1 SH2 domain with high binding affinities. The heterochiral Mb-SH2 structures reveal an unusual binding mode. The D-Mbs are protease-resistant, inhibit BCR::ABL1 kinase activity and bind BCR::ABL1 in cell lysates. [ABSTRACT FROM AUTHOR]

Human evolution in groups has given us language. But it has also led to a present where it appears increasingly difficult to understand each other. Language can be used to clarify or to obscure; it can unite or separate. It is as if we speak different languages. (This is written in English as my own second language as a German.) Can thinking about actual linguistic differences help? A foreign language can be a barrier to communication—and learning or translating the language can become a bridge. Similarly, on a personal level (and in psychotherapy), a second language can be used defensively, when it creates a distance to the internal world—and it can be used creatively to rethink it. Group analysis in particular is faced with this dual potential, when members do not all share the same background. Foulkes himself had to struggle with the English language, and (I suggest) turned the challenge into an opportunity for creative new ideas. Foulkes's concept of translation embodies this creativity and carries it into the group-analytic model. This specific Foulkesian translation originates in the group-analytic situation and goes beyond the polarity of the passively translated and the active translator. The mutual task is unavoidable in our polyphonic international group of GASi. [ABSTRACT FROM AUTHOR]

The study of drugs of natural origin that increase endurance and/or accelerate recovery is an integral part of sports medicine and physiology. In this paper, decaffeinated green tea extract (GTE) and two ammonium salts—chloride (ACL) and carbonate (ACR)—were tested individually and in combination with GTE as stimulants of physical performance in a forced swimming rat experimental model. The determined parameters can be divided into seven blocks: functional (swimming duration); biochemistry of blood plasma; biochemistry of erythrocytes; hematology; immunology; gene expression of slow- and fast-twitch muscles (m. soleus, SOL, and m. extensor digitorum longus, EDL, respectively); and morphometric indicators of slow- and fast-twitch muscles. Regarding the negative control (intact animals), the maximum number of changes in all blocks of indicators was recorded in the GTE + ACR group, whose animals showed the maximum functional result and minimum lactate values on the last day of the experiment. Next, in terms of the number of changes, were the groups ACR, ACL, GTE + ACL, GTE and NaCl (positive control). In general, the number of identified adaptive changes was proportional to the functional state of the animals of the corresponding groups, in terms of the duration of the swimming load in the last four days of the experiment. However, not only the total number but also the qualitative composition of the identified changes is of interest. The results of a comparative analysis suggest that, in the model of forced swimming we developed, GTE promotes restoration of the body and moderate mobilization of the immune system, while small doses of ammonium salts, especially ammonium carbonate, contribute to an increase in physical performance, which is associated with satisfactory restoration of skeletal muscles and the entire body. The combined use of GTE with ammonium salts does not give a clearly positive effect. [ABSTRACT FROM AUTHOR]

Background: Chronic liver diseases such as hepatic tumors can affect the brain through the liver–brain axis, leading to neurotransmitter dysregulation and behavioral changes. Cancer patients suffer from fatigue, which can be associated with sleep disturbances. Sleep is regulated via two interlocked mechanisms: homeostatic regulation and the circadian system. In mammals, the hypothalamic suprachiasmatic nucleus (SCN) is the key component of the circadian system. It generates circadian rhythms in physiology and behavior and controls their entrainment to the surrounding light/dark cycle. Neuron–glia interactions are crucial for the functional integrity of the SCN. Under pathological conditions, oxidative stress can compromise these interactions and thus circadian timekeeping and entrainment. To date, little is known about the impact of peripheral pathologies such as hepatocellular carcinoma (HCC) on SCN. Materials and Methods: In this study, HCC was induced in adult male mice. The key neuropeptides (vasoactive intestinal peptide: VIP, arginine vasopressin: AVP), an essential component of the molecular clockwork (Bmal1), markers for activity of neurons (c-Fos), astrocytes (GFAP), microglia (IBA1), as well as oxidative stress (8-OHdG) in the SCN were analyzed by immunohistochemistry at four different time points in HCC-bearing compared to control mice. Results: The immunoreactions for VIP, Bmal1, GFAP, IBA1, and 8-OHdG were increased in HCC mice compared to control mice, especially during the activity phase. In contrast, c-Fos was decreased in HCC mice, especially during the late inactive phase. Conclusions: Our data suggest that HCC affects the circadian system at the level of SCN. This involves an alteration of neuropeptides, neuronal activity, Bmal1, activation of glia cells, and oxidative stress in the SCN. [ABSTRACT FROM AUTHOR]

Abstract Molecular networking connects mass spectra of molecules based on the similarity of their fragmentation patterns. However, during ionization, molecules commonly form multiple ion species with different fragmentation behavior. As a result, the fragmentation spectra of these ion species often remain unconnected in tandem mass spectrometry-based molecular networks, leading to redundant and disconnected sub-networks of the same compound classes. To overcome this bottleneck, we develop Ion Identity Molecular Networking (IIMN) that integrates chromatographic peak shape correlation analysis into molecular networks to connect and collapse different ion species of the same molecule. The new feature relationships improve network connectivity for structurally related molecules, can be used to reveal unknown ion-ligand complexes, enhance annotation within molecular networks, and facilitate the expansion of spectral reference libraries. IIMN is integrated into various open source feature finding tools and the GNPS environment. Moreover, IIMN-based spectral libraries with a broad coverage of ion species are publicly available.

Abstract The physical and mechanical properties of foamed geopolymers were determined. The geopolymers were made with two different metakaolins (from Metacaulim do Brasil - MB, and Pantano Grande/RS - MPG) as precursors, with NaOH and Na2SiO3 as activators, and with the addition of foam, which was produced with the foaming agent diethanolamide of coconut fatty acid with a minimum of 80% concentration. Also, two times (2.5 and 4 h) were used for the calcination of MPG at 750 °C. The results showed that all factors (precursors type, alkali content, silica modulus, and foam content) had a significant influence on the response variables, which presented the following variations: compressive strength of 0.36 to 3.23 MPa; thermal conductivity from 0.22 to 0.42 W/(m.K); saturated bulk density from 1176 to 1364 kg/m3; dry bulk density of 619 to 864 kg/m3; air void from 46.4% to 62.5%; and water absorption from 55.7% to 95.4%. It was also concluded that the precursor type was the factor that had the most influence on the properties of foamed geopolymers, with MPG calcined for 4 h being the best, as greater compressive strength and low thermal conductivity were obtained.

In early summer 1980, radical geography students rallied around the slogan „Geografe nüme schlafe!“ („Geographers, stop sleeping!“) to take part in the radical youth movement that shook the city of Zurich at that time. In turn, these activist students brought these struggles back into the university and the geography department, where they confronted the professorate with their demands for a new curriculum. This paper argues that the antagonistic Stimmung, in which these struggles took place, produced a radical „thought style“ that flourished in a specific constellation of „thought events“: a prominent theory seminar in 1980, the AK WissKri, a network of radical geography students, the „Geoscope“ journal and, finally, a number of diploma theses on feminist, urban and historical geography. In these thought events, a radical geography materialized outside and beyond the mainstream of German language geography. Building on archival material and narrative interviews, this paper documents these student initiatives for a radical geography, and illustrates the precarious conditions of possibility of radical geography, in Zurich, and beyond.