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The decomposition of organic matter is essential for sustaining the health of freshwater ecosystems by enabling nutrient recycling, sustaining food webs, and shaping habitat conditions, which collectively enhance ecosystem resilience and productivity. Bacteria and fungi play a crucial role in this process by breaking down coarse particulate organic matter (CPOM), such as leaf litter, into nutrients available for other organisms. However, the specific contribution of bacteria and their functional interactions with fungi in freshwater sediments have yet to be thoroughly explored. In the following study, we enriched organic matter through the addition of alder ( Alnus glutinosa ) leaves into artificial stream channels (AquaFlow mesocosms). We then investigated enzyme expression, metabolic pathways, and community composition of fungi and bacteria involved in the degradation of CPOM through metatranscriptomics and amplicon sequencing. Enzymes involved in the degradation of lignin, cellulose, and hemicellulose were selectively upregulated with increased organic matter. Analysis of ITS and 16S rRNA gene sequences revealed that during decomposition, fungal communities were predominantly composed of Basidiomycota and Ascomycota , while bacterial communities were largely dominated by Pseudomonadota and Bacteroidota . The similar gene expression patterns of CPOM degradation related enzymes observed between bacteria and fungi indicate potential functional interaction between these microbial groups. This correlation in enzyme expression may indicate that bacteria and fungi are jointly involved in the breakdown of coarse particulate organic matter, potentially through mutualistic interaction. This study uncovers the specific enzymatic activities of bacteria and fungi and the importance of microbial interactions in organic matter decomposition, revealing their central role in facilitating nutrient cycling and maintaining the ecological health and stability of freshwater ecosystems.

Microbial predator–prey interactions play a crucial role in aquatic food webs. Bacterivorous protists not only regulate the quantity and biomass of bacterial populations but also profoundly influence the structure of bacterial communities. Consequently, alterations in both the quantity and quality of protist bacterivory can influence the overall structure of aquatic food webs. While it is well-documented that changes in environmental conditions or the occurrence of abiotic stressors can lead to shifts in microbial community compositions, the impact of such disturbances on food selection remains unknown. Here, we investigated the effects of elevated temperature and salinization on food selectivity of heterotrophic nanoflagellates by monitoring the uptake of preselected target bacteria via catalyzed reporter deposition fluorescence in situ hybridization and fluorescence microscopy. Our results indicate that salinization, but not increased temperature, significantly increased the flagellates’ selection against Microbacterium lacusdiani (Actinomycetota). However, the effect of the reduced grazing pressure was counterbalanced by the negative effect of increased salinity on the growth of Actinomycetota. Our results suggest that the effect of stressors on the feeding behavior of protistan predators may strongly affect the composition of their prey community, when bacterial taxa are concerned that are less sensitive to the particular stressor.

The round goby, Neogobius melanostomus, is a Ponto-Caspian fish considered as an invasive species in a wide range of aquatic ecosystems. To understand the role that parasites may play in its successful invasion across Western Europe, we investigated the parasitic diversity of the round goby along its invasion corridor, from the Danube to the Upper Rhine rivers, using data from literature and a molecular barcoding approach, respectively. Among 1666 parasites extracted from 179 gobies of the Upper Rhine, all of the 248 parasites barcoded on the c oxidase subunit I gene were identified as Pomphorhynchus laevis. This lack of macroparasite diversity was interpreted as a loss of parasites along its invasion corridor without spillback compensation. The genetic diversity of P. laevis was represented by 33 haplotypes corresponding to a haplotype diversity of 0·65 ± 0·032, but a weak nucleotide diversity of 0·0018 ± 0·00015. Eight of these haplotypes were found in 88·4% of the 248 parasites. These haplotypes belong to a single lineage so far restricted to the Danube, Vistula and Volga rivers (Eastern Europe). This result underlines the exotic status of this Ponto-Caspian lineage in the Upper Rhine, putatively disseminated by the round goby along its invasion corridor.

Summary Identifying which abiotic and biotic factors determine microbial community assembly is crucial to understand ecological processes and predict how communities will respond to environmental change. While global surveys aim at addressing this question in the world’s oceans, equivalent studies in large freshwater systems are virtually lacking. Being the oldest, deepest and most voluminous freshwater lake on Earth, Lake Baikal offers a unique opportunity to test the effect of horizontal versus vertical gradients in community structure. Here, we characterized the structure of planktonic microbial eukaryotic communities (0.2-30 µm cell size) along a North-South latitudinal gradient (∼600 km) from samples collected in coastal and pelagic waters and from surface to the deepest zones (5-1400 m) using an 18S rRNA gene metabarcoding approach. Our results show complex and diverse protist communities dominated by alveolates (ciliates and dinoflagellates), ochrophytes and holomycotan lineages, with cryptophytes, haptophytes, katablepharids and telonemids in moderate abundance and many low-frequency lineages, including several typical marine members, such as diplonemids, syndinians and radiolarians. Depth had a strong significant effect on protist community stratification. By contrast, the effect of the latitudinal gradient was marginal and no significant difference was observed between coastal and surface open water communities. Co-occurrence network analyses showed that epipelagic communities are much more interconnected than meso- and bathypelagic communities and suggest specific biotic interactions between autotrophic, heterotrophic and parasitic lineages that influence protist community structure. Since climate change is rapidly affecting Siberia and Lake Baikal, our comprehensive protist survey constitutes a useful reference to monitor ongoing community shifts. Originality and Significance Statement Lake Baikal is the oldest, deepest and most voluminous freshwater lake on Earth, offering a unique opportunity to test the effects of horizontal versus vertical gradients on microbial community structure. Using a metabarcoding approach, we studied planktonic microbial eukaryotes from Baikal water columns (5 up to 1,400 m depth) across a North-South latitudinal gradient (∼600 km), including coastal and pelagic areas. Our results show that depth has a strong effect on protist community assemblage, but not latitude (minor effect) or coastal vs. open water sites (no effect). Co-occurrence analyses also point to specific biotic interactions as drivers of community structure. This comprehensive survey constitutes a useful reference for monitoring active climate change effects in this ancient lake. Competing Interest Statement The authors have declared no competing interest.

IntroductionInternational medical oncology societies recommended early integration of palliative care to alleviate symptoms, improve quality of life and significantly reduce aggressiveness of care near the end of life, defined as the use of chemotherapy, high rate of hospitalisation/visits to emergency or intensive care unit in the last month of life or death in acute care unit. However, the most appropriate schedule for patient referral is still to be determined. Scores and criteria are debated, with uncontrolled symptoms (pain, dyspnoea, distress, etc) being one of the main indicators. These symptoms are also the leading causes for patients with cancer to seek care in emergency units. Several studies in North America suggested that referral to palliative care from emergency units is feasible and efficient.The aim of this study is to determine if systematic early referral to palliative care in a context of emergency reduces aggressiveness of care near the end of life compared with referral on medical team request.Methods and analysisThis multicentric randomised study plans to enrol patients with a PALLIA-10 score >3 attending unscheduled on-site visits in French comprehensive cancer centres, and allocate them to randomisation (1:1) to receive palliative care systematically (experimental group) or on medical oncology team request (standard group). The primary objective is to compare the proportion of patients meeting at least one criterion of clinical care aggressiveness near the end of life, in each group. Secondary objectives include a description of clinical care aggressiveness components, palliative care requirement (psychologist, social worker, nutritional counselling, etc), patient-reported outcomes (FACT-G7, Hospital Anxiety and Depression Scale, Edmonton Symptoms Assessment System), the place of death and overall survival. Health economics and human and social sciences substudies will be presented.The study needs to include 192 patients (96 patients per arm) to reach a 20% decrease in care aggressiveness in the last month of life from 65% to 45%, with a statistical power of 80%, and a 2-sided type I error rate of 5%, using systematic referral. Considering a 20% rate of dropout or patients still alive at the time of analysis, 240 patients will need to be allocated to randomisation.Ethics and disseminationThis clinical study received approval from the Ethics committee CPP Est III on 25 October 2023, and complies with the MR001 Commission Nationale de l’Informatique et des Libertés (#1994173, 27 September 2016). The first consent was signed on 12 September 2024.Results will be presented and published in international academic journals.Protocol identifierV.2.1 dated 10 July 2024.Trial registration number NCT06150027.

Background The Bcl-3 protein is an atypical member of the inhibitor of -κB family that has dual roles as a transcriptional repressor and a coactivator for dimers of NF-κB p50 and p52. Bcl-3 is expressed in mammary adenocarcinomas and can promote tumorigenesis and survival signaling and has a key role in tumor metastasis. In this study, we have investigated the role of Bcl-3 in the normal mammary gland and impact on tumor pathology. Methods We utilized bcl-3 −/− mice to study mammary gland structure in virgins and during gestation, lactation and early involution. Expression of involution-associated genes and proteins and putative Bcl-3 target genes was examined by qRT-PCR and immunoblot analysis. Cell autonomous branching morphogenesis and collagen I invasion properties of bcl-3 −/− organoids were tested in 3D hydrogel cultures. The role of Bcl-3 in tumorigenesis and tumor pathology was also assessed using a stochastic carcinogen-induced mammary tumor model. Results Bcl-3 −/− mammary glands demonstrated reduced branching complexity in virgin and pregnant mice. This defect was recapitulated in vitro where significant defects in bud formation were observed in bcl-3 −/− mammary organoid cultures. Bcl-3 −/− organoids showed a striking defect in protrusive collective fibrillary collagen I invasion associated with reduced expression of Fzd1 and Twist2. Virgin and pregnant bcl-3 −/− glands showed increased apoptosis and rapid increases in lysosomal cell death and apoptosis after forced weaning compared to WT mice. Bcl-2 and Id3 are strongly induced in WT but not bcl-3 −/− glands in early involution. Tumors in WT mice were predominately adenocarcinomas with NF-κB activation, while bcl-3 −/− lesions were largely squamous lacking NF-κB and with low Bcl-2 expression. Conclusions Collectively, our results demonstrate that Bcl-3 has a key function in mammary gland branching morphogenesis, in part by regulation of genes involved in extracellular matrix invasion. Markedly reduced levels of pro-survival proteins expression in bcl-3 null compared to WT glands 24 h post-weaning indicate that Bcl-3 has a role in moderating the rate of early phase involution. Lastly, a reduced incidence of bcl-3 −/− mammary adenocarcinomas versus squamous lesions indicates that Bcl-3 supports the progression of epithelial but not metaplastic cancers.

Okra is grown globally for its nutritional and economic benefits. Okra seeds ensure continuous production of the crop but challenges of poor production, adaptability and management may not allow the seeds to express their full potential. There are two seed production systems in Cameroon; the informal and formal. In Buea, the informal seed system is used by most farmers for seed production/utilization and farmers are reluctant to use hybrid seeds. This study aimed to assess the informal seed system of okra and evaluate the adaptability of seed produce from informal and formal systems in Buea. A survey and a field experiment were carried out. The designs for the survey and field experiment were stratified random sampling and randomized complete block design respectively. Data collection for the survey was done using questionnaires and other data collection instruments, while for the field experiment, data was collected on germination, vegetative growth parameters, incidence and severity of pests / diseases and yield. Data analysis for the survey was done using descriptive statistics, while data from the field experiment was done using a two-way ANOVA test and treatment means compared using the Tukey test at 5% probability. Results from the survey showed that women (60%) were mostly involved in seed production by mass selection from two landraces identified. Preservation of seeds was mostly done with the use of wood ash (58%) and insects were the major postharvest pest (76%). For the field experiment, at 66 DAP, Yellen recorded the highest significant number of leaves (13.417), leaf area (771.4 cm 2 ) and the number of branches (5.64). Clemson spineless recorded the highest significant incidence (89.9%) and severity for pests / diseases while Kirikou and Landrace recorded the least incidence (0.0%) and severity. Kirikou recorded the highest significant yield (6.0 tons/ha), followed by Landrace (5.3 tons/ha). These findings reveal the performance of the landrace and provide reasons why farmers in Buea are reluctant to use hybrid okra seeds. The Landrace should certainly have adaptable genes, coupled with the autogamous nature of okra which encourages inbreeding for homozygous traits, which are dominant in expression compared to heterozygous traits.

Cellular inhibitor of apoptosis proteins-1 and -2 (cIAP1/2) are integral to regulation of apoptosis and signaling by the tumor necrosis factor (TNF) and related family of receptors. The expression of cIAP2 in tissues is typically low and considered functionally redundant with cIAP1, however cIAP2 can be activated by a variety of cellular stresses. Members of the TNFR family and their ligands have essential roles in mammary gland biology. We have found that cIAP2−/− virgin mammary glands have reduced ductal branching and delayed lobuloalveogenesis in early pregnancy. Post-lactational involution involves two phases where the first phase is reversible and is mediated, in part, by TNFR family ligands. In cIAP2−/− mice mammary glands appeared engorged at mid-lactation accompanied by enhanced autophagic flux and decreased cIAP1 protein expression. Severely stretched myoepithelium was associated with BIM-EL expression and other indicators of anoikis. Within 24 h after forced or natural weaning, cIAP2−/− glands had nearly completed involution. The TNF-related weak inducer of apoptosis (Tweak) which results in degradation of cIAP1 through its receptor, Fn14, began to increase in late lactation and was significantly increased in cIAP2−/− relative to WT mice by 12 h post weaning accompanied by decreased cIAP1 protein expression. Carcinogen/progesterone-induced mammary tumorigenesis was significantly delayed in cIAP2−/− mice and tumors contained high numbers of apoptotic cells. We conclude that cIAP2 has a critical role in the mammary gland wherein it prevents rapid involution induced by milk stasis-induced stress associated with Tweak activation and contributes to the survival of mammary tumor cells.

Background Biofilm formation is an important survival strategy of Salmonella in all environments. By mutant screening, we showed a knock-out mutant of fabR , encoding a repressor of unsaturated fatty acid biosynthesis (UFA), to have impaired biofilm formation. In order to unravel how this regulator impinges on Salmonella biofilm formation, we aimed at elucidating the S . Typhimurium FabR regulon. Hereto, we applied a combinatorial high-throughput approach, combining ChIP-chip with transcriptomics. Results All the previously identified E. coli FabR transcriptional target genes ( fabA , fabB and yqfA ) were shown to be direct S. Typhimurium FabR targets as well. As we found a fabB overexpressing strain to partly mimic the biofilm defect of the fabR mutant, the effect of FabR on biofilms can be attributed at least partly to FabB, which plays a key role in UFA biosynthesis. Additionally, ChIP-chip identified a number of novel direct FabR targets (the intergenic regions between hpaR / hpaG and ddg / ydfZ ) and yet putative direct targets ( i.a. genes involved in tRNA metabolism, ribosome synthesis and translation). Next to UFA biosynthesis, a number of these direct targets and other indirect targets identified by transcriptomics (e.g. ribosomal genes, ompA , ompC , ompX , osmB , osmC, sseI ), could possibly contribute to the effect of FabR on biofilm formation. Conclusion Overall, our results point at the importance of FabR and UFA biosynthesis in Salmonella biofilm formation and their role as potential targets for biofilm inhibitory strategies.

This Phase I, open‐label, two‐group, fixed‐sequence study evaluated the pharmacokinetics and safety of AL‐335, odalasvir, and simeprevir in healthy subjects. Group 1 (n = 16) received AL‐335 800 mg once daily (QD) (days 1‐3, 11‐13, and 21‐23), simeprevir 150 mg QD (days 4‐23), and odalasvir 150 mg (day 14) followed by 50 mg QD (days 15‐23). Group 2 (n = 16) received the same AL‐335 regimen as in Group 1 plus odalasvir 150 mg (day 4) followed by 50 mg QD (days 5‐23) and simeprevir 150 mg QD (days 14‐23). Blood samples were collected to determine plasma concentrations of AL‐335 (prodrug) and its metabolites, ALS‐022399 (monophosphate precursor) and ALS‐022227 (parent nucleoside), odalasvir, and simeprevir. Thirty‐two subjects were enrolled. Odalasvir and simeprevir given alone, or in combination, increased AL‐335 area under plasma concentration‐time curve over 24 hours (AUC0‐24 h) 3‐, 4‐, and 7‐ to 8‐fold, respectively; ALS‐022399 AUC0‐24 h increased 2‐, 2‐, and 3‐fold, respectively. Simeprevir had no effect on ALS‐022227 AUC0‐24 h, whereas odalasvir with/without simeprevir increased ALS‐022227 AUC0‐24 h 1.5‐fold. AL‐335 had no effect on odalasvir or simeprevir pharmacokinetics. Odalasvir and simeprevir AUC0‐24 h increased 1.5‐ to 2‐fold for both drugs when coadministered irrespective of AL‐335 coadministration. Study medications were well tolerated with no serious adverse events. One subject prematurely discontinued study drugs (unrelated event). This study defined the preliminary pharmacokinetic and safety profiles of the combination of AL‐335, odalasvir, and simeprevir in healthy subjects. These data support the further evaluation of this combination for the treatment of chronic hepatitis C virus infection.