Microplastic pollution and nutrient enrichment shift the diet of freshwater macroinvertebrates.

Microplastic pollution poses a global threat to freshwater ecosystems, with laboratory experiments indicating potential toxic impacts through chemical toxicity, physical abrasion, and false satiation. Bioplastics have emerged as a potential greener alternative to traditional oil-based plastics. Yet, their environmental effects remain unclear, particularly at scales relevant to the natural environment. Additionally, the interactive impacts of microplastics with other environmental stressors, such as nutrient enrichment, are poorly understood and rarely studied. Under natural conditions organisms might be able to mitigate the toxic effects of microplastics by shifting their diet, but this ability may be compromised by other stressors. This study combines an outdoor mesocosm experiment and stable isotope analysis to determine changes in the trophic niches of three freshwater invertebrate species exposed to conventional (HDPE) and bio-based biodegradable (PLA) microplastics at two concentrations, both independently and combined with nutrient enrichment. Exposure to microplastics altered the isotopic niches of two of the invertebrate species, with nutrient enrichment mediating this effect. Moreover, the effects of microplastics were consistent regardless of their type or concentration. Under enriched conditions, two of the species exposed to microplastics shifted to a specialised diet compared with controls, whereas little difference was observed between the isotopic niches of those exposed to microplastic and controls under ambient nutrient conditions. Additionally, PLA was estimated to support 24 % of the diet of one species, highlighting the potential assimilation of bioplastics by biota and possible implications. Overall, these findings suggest that the toxic effects of microplastics suggested from laboratory studies might not manifest under real-world conditions. However, this study does demonstrate that subtle sublethal effects occur even at environmentally realistic microplastic concentrations. The crucial role of nutrient enrichment in mediating microplastic effects underscores the importance of considering microplastic pollution in the context of other environmental stressors.

Time series of freshwater macroinvertebrate abundances and site characteristics of European streams and rivers.

Freshwater macroinvertebrates are a diverse group and play key ecological roles, including accelerating nutrient cycling, filtering water, controlling primary producers, and providing food for predators. Their differences in tolerances and short generation times manifest in rapid community responses to change. Macroinvertebrate community composition is an indicator of water quality. In Europe, efforts to improve water quality following environmental legislation, primarily starting in the 1980s, may have driven a recovery of macroinvertebrate communities. Towards understanding temporal and spatial variation of these organisms, we compiled the TREAM dataset (Time seRies of European freshwAter Macroinvertebrates), consisting of macroinvertebrate community time series from 1,816 river and stream sites (mean length of 19.2 years and 14.9 sampling years) of 22 European countries sampled between 1968 and 2020. In total, the data include >93 million sampled individuals of 2,648 taxa from 959 genera and 212 families. These data can be used to test questions ranging from identifying drivers of the population dynamics of specific taxa to assessing the success of legislative and management restoration efforts.

Effect of oral tryptamines on the gut microbiome of rats-a preliminary study.

Background: Psilocybin and related tryptamines have come into the spotlight in recent years as potential therapeutics for depression. Research on the mechanisms of these effects has historically focused on the direct effects of these drugs on neural processes. However, in addition to such neural effects, alterations in peripheral physiology may also contribute to their therapeutic effects. In particular, substantial support exists for a gut microbiome-mediated pathway for the antidepressant efficacy of other drug classes, but no prior studies have determined the effects of tryptamines on microbiota. Methods: To address this gap, in this preliminary study, male Long Evans rats were treated with varying dosages of oral psilocybin (0.2 or 2 mg/kg), norbaeocystin (0.25 or 2.52 mg/kg), or vehicle and their fecal samples were collected 1 week and 3 weeks after exposure for microbiome analysis using integrated 16S ribosomal DNA sequencing to determine gut microbiome composition. Results: We found that although treatment with neither psilocybin nor norbaeocystin significantly affected overall microbiome diversity, it did cause significant dose- and time-dependent changes in bacterial abundance at the phylum level, including increases in Verrucomicrobia and Actinobacteria, and decreases in Proteobacteria. Conclusion and Implications: These preliminary findings support the idea that psilocybin and other tryptamines may act on the gut microbiome in a dose- and time-dependent manner, potentially identifying a novel peripheral mechanism for their antidepressant activity. The results from this preliminary study also suggest that norbaeocystin may warrant further investigation as a potential antidepressant, given the similarity of its effects to psilocybin.

Evaluation of TrpM and PsiD substrate promiscuity reveals new biocatalytic capabilities.

N-methylated tryptamines, such as the hallucinogenic natural products, psilocybin and N,N-dimethyltryptamine (DMT), are gaining interest from the medical community due to their potential as next generation treatments for mental health disorders. The clinical relevance of these compounds has driven scientists to develop biosynthetic production routes to a number of tryptamine drug candidates, and efforts are ongoing to expand and further develop these biosynthetic capabilities. To that end, we have further characterized the substrate preferences of two enzymes involved in tryptamine biosynthesis: TrpM, a tryptophan N-methyltransferase from Psilocybe serbica, and PsiD, the gateway decarboxylase of the psilocybin biosynthesis pathway. Here, we show that TrpM can N-methylate the non-native amino acid substrate, 4-hydroxytryptophan, a key intermediate in the Escherichia coli-based recombinant psilocybin biosynthesis pathway. However, the ability to incorporate TrpM into a functional psilocybin biosynthesis pathway was thwarted by PsiD's inability to use N,N-dimethyl-4-hydroxytryptophan as substrate, under the culturing conditions tested, despite demonstrating activity on N-methylated and 4-hydroxylated tryptophan derivatives individually. Taken together, this work expands upon the known substrates for TrpM and PsiD, further increasing the diversity of tryptamine biosynthetic products.

Pharmacological and behavioural effects of tryptamines present in psilocybin-containing mushrooms.

BACKGROUND AND PURPOSE: Demand for new antidepressants has resulted in a re-evaluation of the therapeutic potential of psychedelic drugs. Several tryptamines found in psilocybin-containing "magic" mushrooms share chemical similarities with psilocybin. Early work suggests they may share biological targets. However, few studies have explored their pharmacological and behavioural effects. EXPERIMENTAL APPROACH: We compared baeocystin, norbaeocystin and aeruginascin with psilocybin to determine if they are metabolized by the same enzymes, similarly penetrate the blood-brain barrier, serve as ligands for similar receptors and modulate behaviour in rodents similarly. We also assessed the stability and optimal storage and handling conditions for each compound. KEY RESULTS: In vitro enzyme kinetics assays found that all compounds had nearly identical rates of dephosphorylation via alkaline phosphatase and metabolism by monoamine oxidase. Further, we found that only the dephosphorylated products of baeocystin and norbaeocystin crossed a blood-brain barrier mimetic to a similar degree as the dephosphorylated form of psilocybin, psilocin. The dephosphorylated form of norbaeocystin was found to activate the 5-HT2A receptor with similar efficacy to psilocin and norpsilocin in in vitro cell imaging assays. Behaviourally, only psilocybin induced head twitch responses in rats, a marker of 5-HT2A-mediated psychedelic effects and hallucinogenic potential. However, like psilocybin, norbaeocystin improved outcomes in the forced swim test. All compounds caused minimal changes to metrics of renal and hepatic health, suggesting innocuous safety profiles. CONCLUSIONS AND IMPLICATIONS: Collectively, this work suggests that other naturally occurring tryptamines, especially norbaeocystin, may share overlapping therapeutic potential with psilocybin, but without causing hallucinations.

Exploring the potential of biofiltration for mitigating harmful gaseous emissions from small or old landfills: a review.

Landfills are widely employed as the primary means of solid waste disposal. However, this practice generates landfill gas (LFG) which contains methane (CH4), a potent greenhouse gas, as well as various volatile organic compounds and volatile inorganic compounds. These emissions from landfills contribute to approximately 25% of the total atmospheric CH4, indicating the imperative need to valorize or treat LFG prior to its release into the atmosphere. This review first aims to outline landfills, waste disposal and valorization, conventional gas treatment techniques commonly employed for LFG treatment, such as flares and thermal oxidation. Furthermore, it explores biotechnological approaches as more technically and economically feasible alternatives for mitigating LFG emissions, especially in the case of small and aged landfills where CH4 concentrations are often below 3% v/v. Finally, this review highlights biofilters as the most suitable biotechnological solution for LFG treatment and discusses several advantages and challenges associated with their implementation in the landfill environment.

Water for agriculture: more crop per drop.

Global crop production in agriculture depends on water availability. Future scenarios predict increasing occurrence of flash floods and rapidly developing droughts accompanied by heatwaves in humid regions that rely on rain-fed agriculture. It is challenging to maintain high crop yields, even in arid and drought-prone regions that depend on irrigation. The average water demand of crops varies significantly, depending on plant species, development stage, and climate. Most crops, such as maize and wheat, require relatively more water during the vegetative phase compared to the ripening phase. In this review, we explain WUE and options to improve water use and thus crop yield. Nutrient management might represent another possibility to manipulate water uptake and use by plants. An emerging topic involves agroforest co-cultivation, where trees in the system facilitate water transfer through hydraulic lift, benefiting neighbouring crops. Other options to enhance crop yield per water use are discussed.

Discovery and Preclinical Characterization of BIIB129, a Covalent, Selective, and Brain-Penetrant BTK Inhibitor for the Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic disease with an underlying pathology characterized by inflammation-driven neuronal loss, axonal injury, and demyelination. Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase and member of the TEC family of kinases, is involved in the regulation, migration, and functional activation of B cells and myeloid cells in the periphery and the central nervous system (CNS), cell types which are deemed central to the pathology contributing to disease progression in MS patients. Herein, we describe the discovery of BIIB129 (25), a structurally distinct and brain-penetrant targeted covalent inhibitor (TCI) of BTK with an unprecedented binding mode responsible for its high kinome selectivity. BIIB129 (25) demonstrated efficacy in disease-relevant preclinical in vivo models of B cell proliferation in the CNS, exhibits a favorable safety profile suitable for clinical development as an immunomodulating therapy for MS, and has a low projected total human daily dose.

Inconclusive decisions and error rates in forensic science.

In recent years, there has been discussion and controversy relating to the treatment of inconclusive decisions in forensic feature comparison disciplines when considering the reliability of examination methods and results. In this article, we offer a brief review of the various viewpoints and suggestions that have been recently put forth, followed by a solution that we believe addresses the treatment of inconclusive decisions. We consider the issues in the context of method conformance and method performance as two distinct concepts, both of which are necessary for the determination of reliability. Method conformance relates to an assessment of whether the outcome of a method is the result of the analyst's adherence to the procedures that define the method. Method performance reflects the capacity of a method to discriminate between different propositions of interest (e.g., mated and non-mated comparisons). We then discuss implications of these issues for the forensic science community.

A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast.

Here we use single-cell RNA sequencing to compile a human breast cell atlas assembled from 55 donors that had undergone reduction mammoplasties or risk reduction mastectomies. From more than 800,000 cells we identified 41 cell subclusters across the epithelial, immune and stromal compartments. The contribution of these different clusters varied according to the natural history of the tissue. Age, parity and germline mutations, known to modulate the risk of developing breast cancer, affected the homeostatic cellular state of the breast in different ways. We found that immune cells from BRCA1 or BRCA2 carriers had a distinct gene expression signature indicative of potential immune exhaustion, which was validated by immunohistochemistry. This suggests that immune-escape mechanisms could manifest in non-cancerous tissues very early during tumor initiation. This atlas is a rich resource that can be used to inform novel approaches for early detection and prevention of breast cancer.

Versican Associates with Tumor Immune Phenotype and Limits T-cell Trafficking via Chondroitin Sulfate.

Immunotherapies for cancers of epithelial origin have limited efficacy, and a growing body of evidence links the composition of extracellular matrix (ECM) with the likelihood of a favorable response to treatment. The ECM may be considered an immunologic barrier, restricting the localization of cytotoxic immune cells to stromal areas and inhibiting their contact with tumor cells. Identifying ECM components of this immunologic barrier could provide targets that whether degraded in situ may support antitumor immunity and improve immunotherapy response. Using a library of primary triple-negative breast cancer tissues, we correlated CD8+ T-cell tumor contact with ECM composition and identified a proteoglycan, versican (VCAN), as a putative member of the immunologic barrier. Our analysis reveals that CD8+ T-cell contact with tumor associates with the location of VCAN expression, the specific glycovariant of VCAN [defined through the pattern of posttranslational attachments of glycosaminoglycans (GAG)], and the cell types that produce the variant. In functional studies, the isomers of chondroitin sulfate presented on VCAN have opposing roles being either supportive or inhibiting of T-cell trafficking, and removal of the GAGs ameliorates these effects on T-cell trafficking. Overall, we conclude that VCAN can either support or inhibit T-cell trafficking within the tumor microenvironment depending on the pattern of GAGs present, and that VCAN is a major component of the ECM immunologic barrier that defines the type of response to immunotherapy. SIGNIFICANCE: The response to immunotherapy has been poor toward solid tumors despite immune cells infiltrating into the tumor. The ECM has been associated with impacting T-cell infiltration toward the tumor and in this article we have identified VCAN and its structural modification, chondroitin sulfate as having a key role in T-cell invasion.

'Low' faecal immunochemical test (FIT) colorectal cancer: a 4-year comparison of the Nottingham '4F' protocol with FIT10 in symptomatic patients.

AIM: The aim of this work was to evaluate colorectal cancer (CRC) outcomes after 'low' (sub-threshold) faecal immunochemical test (FIT) results in symptomatic patients tested in primary care. METHOD: This work comprised a retrospective audit of 35 289 patients with FIT results who had consulted their general practitioner with lower gastrointestinal symptoms and had subsequent CRC diagnoses. The Rapid Colorectal Cancer Diagnosis pathway was introduced in November 2017 to allow incorporation of FIT into clinical practice. The local '4F' protocol combined FIT results with blood tests and digital rectal examination (DRE): FIT, full blood count, ferritin and finger [DRE]. The outcome used was detection rates of CRC, missed CRC and time to diagnosis in local 4F protocols for patients with a subthreshold faecal haemoglobin (fHb) result compared with thresholds of 10 and 20 µg Hb/g faeces. RESULTS: A single threshold of 10 µg Hb/g faeces identifies a population in whom the risk of CRC is 0.2%, but this would have missed 63 (10.5%) of 599 CRCs in this population. The Nottingham 4F protocol would have missed fewer CRCs [42 of 599 (7%)] despite using a threshold of 20 µg Hb/g faeces for patients with normal blood tests. Subthreshold FIT results in patients subsequently diagnosed with a palpable rectal tumour yielded the longest delays in diagnosis. CONCLUSION: A combination of FIT with blood results and DRE (the 4F protocol) reduced the risk of missed or delayed diagnosis. Further studies on the impact of such protocols on the diagnostic accuracy of FIT are expected. The value of adding blood tests to FIT may be restricted to specific parts of the fHb results spectrum.

Freshwater invertebrate responses to fine sediment stress: A multi-continent perspective.

Excessive fine sediment (particles <2 mm) deposition in freshwater systems is a pervasive stressor worldwide. However, understanding of ecological response to excess fine sediment in river systems at the global scale is limited. Here, we aim to address whether there is a consistent response to increasing levels of deposited fine sediment by freshwater invertebrates across multiple geographic regions (Australia, Brazil, New Zealand and the UK). Results indicate ecological responses are not globally consistent and are instead dependent on both the region and the facet of invertebrate diversity considered, that is, taxonomic or functional trait structure. Invertebrate communities of Australia were most sensitive to deposited fine sediment, with the greatest rate of change in communities occurring when fine sediment cover was low (below 25% of the reach). Communities in the UK displayed a greater tolerance with most compositional change occurring between 30% and 60% cover. In both New Zealand and Brazil, which included the most heavily sedimented sampled streams, the communities were more tolerant or demonstrated ambiguous responses, likely due to historic environmental filtering of invertebrate communities. We conclude that ecological responses to fine sediment are not generalisable globally and are dependent on landscape filters with regional context and historic land management playing important roles.

Simultaneous glucose and xylose utilization by an Escherichia coli catabolite repression mutant.

As advances are made toward the industrial feasibility of mass-producing biofuels and commodity chemicals with sugar-fermenting microbes, high feedstock costs continue to inhibit commercial application. Hydrolyzed lignocellulosic biomass represents an ideal feedstock for these purposes as it is cheap and prevalent. However, many microbes, including Escherichia coli, struggle to efficiently utilize this mixture of hexose and pentose sugars due to the regulation of the carbon catabolite repression (CCR) system. CCR causes a sequential utilization of sugars, rather than simultaneous utilization, resulting in reduced carbon yield and complex process implications in fed-batch fermentation. A mutant of the gene encoding the cyclic AMP receptor protein, crp*, has been shown to disable CCR and improve the co-utilization of mixed sugar substrates. Here, we present the strain construction and characterization of a site-specific crp* chromosomal mutant in E. coli BL21 star (DE3). The crp* mutant strain demonstrates simultaneous consumption of glucose and xylose, suggesting a deregulated CCR system. The proteomics further showed that glucose was routed to the C5 carbon utilization pathways to support both de novo nucleotide synthesis and energy production in the crp* mutant strain. Metabolite analyses further show that overflow metabolism contributes to the slower growth in the crp* mutant. This highly characterized strain can be particularly beneficial for chemical production by simultaneously utilizing both C5 and C6 substrates from lignocellulosic biomass.IMPORTANCEAs the need for renewable biofuel and biochemical production processes continues to grow, there is an associated need for microbial technology capable of utilizing cheap, widely available, and renewable carbon substrates. This work details the construction and characterization of the first B-lineage Escherichia coli strain with mutated cyclic AMP receptor protein, Crp*, which deregulates the carbon catabolite repression (CCR) system and enables the co-utilization of multiple sugar sources in the growth medium. In this study, we focus our analysis on glucose and xylose utilization as these two sugars are the primary components in lignocellulosic biomass hydrolysate, a promising renewable carbon feedstock for industrial bioprocesses. This strain is valuable to the field as it enables the use of mixed sugar sources in traditional fed-batch based approaches, whereas the wild-type carbon catabolite repression system leads to biphasic growth and possible buildup of non-preferential sugars, reducing process efficiency at scale.

Evidence of successful recruitment of non-native pink salmon Oncorhynchus gorbuscha in Iceland.

In mid-May 2022, pink salmon Oncorhynchus gorbuscha smolts were caught in the rivers Botnsá, Grímsá, and Langá in Iceland. This observation provides the first evidence of successful spawning and the completion of the freshwater phase of the life cycle in Icelandic rivers. It is the most western record of O. gorbuscha smolts in Europe, further west than Russia, Norway, and the UK. Smolts originating from Iceland potentially support the recruitment of this species in the North Atlantic and may lead to the establishment of a self-sustaining population in Iceland.

Unlocking the biosynthesis of psychedelic-inspired indolethylamines.

A recent report by Chen et al. describes the discovery of RmNMT, a highly active and promiscuous tryptamine N-methyltransferase from the cane toad, Rhinella marina. N,N-dimethyltryptamine derivatives produced by this enzyme were then evaluated for their potential to serve as next-generation treatments for mental health disorders.

Characterizing obesity in a large health care delivery system.

OBJECTIVES: To characterize the prevalence of obesity and associated health care use within an integrated health care system in California. STUDY DESIGN: Cross-sectional study using electronic health records. METHODS: Primary care patients 18 years and older receiving care at Sutter Health between 2015 and 2020 were included in the study. Obesity was classified and health care utilization was ascertained at index and during the follow-up periods. Differences in prevalence by demographic and clinical characteristics among patients with and without obesity were assessed. Logistic regression was used to estimate the relationship between obesity class and health care utilization (outpatient encounters). RESULTS: Of the 1,094,790 primary care patients included in the analysis, 35% were classified as having obesity, defined as a body mass index of 30 kg/m2 or more or 25 kg/m2 or more for Asian individuals. Obesity prevalence was greater in Hispanic patients (46%) than in non-Hispanic White patients (30%). Patients without obesity had fewer outpatient visits (mean [SD], 3.7 [3.8]) than those with class 1 (4.1 [4.0]), class 2 (4.6 [4.4]), and class 3 (5.2 [4.8]) obesity. In the fully adjusted regression model, the odds of being a high utilizer among patients with obesity were 1.1 (class 1), 1.2 (class 2), and 1.3 (class 3) times that of patients without obesity (P < .001). CONCLUSION: Obesity prevalence is high among patients in the Sutter Health system, varying by race/ethnicity, and was associated with increased outpatient visit utilization. There is a need for greater awareness of the impact of obesity and the specific patient populations affected by the disease.