Changes In Abundance Research Articles

Intracellular pH dynamics respond to microenvironment stiffening and mediate vasculogenic mimicry through β-catenin.

Dysregulated intracellular pH (pHi) dynamics and an altered tumor microenvironment have emerged as drivers of cancer cell phenotypes. However, the molecular integration between the physical properties of the microenvironment and dynamic intracellular signaling responses remains unclear. Here, we use two metastatic cell models, one breast and one lung, to assess pHi response to varying extracellular matrix (ECM) stiffness. To experimentally model ECM stiffening, we use two tunable-stiffness hydrogel systems: Matrigel and hyaluronic acid (HA) gels, which mimic the increased protein secretion and crosslinking associated with ECM stiffening. We find that single-cell pHi decreases with increased ECM stiffness in both hydrogel systems and both metastatic cell types. We also observed that stiff ECM promotes vasculogenic mimicry (VM), a phenotype associated with metastasis and resistance. Importantly, we show that decreased pHi is both a necessary and sufficient mediator of VM, as raising pHi on stiff ECM reduces VM phenotypes and lowering pHi on soft ECM drives VM. We characterize β-catenin as a pH-dependent molecular mediator of pH-dependent VM, where stiffness-driven changes in β-catenin abundance can be overridden by increased pHi. We uncover a dynamic relationship between matrix stiffness and pHi, thus suggesting pHi dynamics can override mechanosensitive cell responses to the extracellular microenvironment.

Intensive professional vehicle-based shooting provides local control of invasive rusa deer in a peri-urban landscape

Non-native deer are becoming increasingly common in peri-urban landscapes, where they pose a risk to the health and wellbeing of people. Professional vehicle-based shooting is commonly used to control deer populations in these complex landscapes, but the effectiveness and cost of this method have seldom been evaluated. We analyzed the effectiveness and cost of using professional vehicle-based shooting to reduce the abundance and impacts of non-native rusa deer (Cervus timorensis) in a peri-urban landscape in Wollongong, eastern Australia, during 2011–2021. We incorporated the results from an independent monitoring program into a Bayesian joint-likelihood framework to model spatio-temporal changes in rusa deer abundance. Finally, we used our findings to assess the effect of the management program on the number of complaints from the residents. After eleven years and the removal of 4701 rusa deer from Wollongong LGA (712 km2), deer abundance did not change in 74.7% of the area, decreased in 19.4% of the area (mostly in and around the sites where the professional shooting occurred), and increased in 5.9% of the area. Shooting was most cost-effective during winter when the longer hours of darkness meant that shooters could visit more sites. In contrast to deer abundance, the probability of residents complaining about deer increased in space and time. Our study shows that professional vehicle-based shooting can locally reduce the abundance of invasive deer in a peri-urban landscape, providing that sufficient control effort is expended. We suggest that shooting effort is currently too thinly spread across this peri-urban landscape, and that concentrating shooting effort on the areas of greatest deer abundance and resident complaints might be a more cost-effective strategy for managing invasive deer in peri-urban landscapes.

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.

Cooperative growth in microbial communities is a driver of multistability

Microbial communities often exhibit more than one possible stable composition for the same set of external conditions. In the human microbiome, these persistent changes in species composition and abundance are associated with health and disease states, but the drivers of these alternative stable states remain unclear. Here we experimentally demonstrate that a cross-kingdom community, composed of six species relevant to the respiratory tract, displays four alternative stable states each dominated by a different species. In pairwise coculture, we observe widespread bistability among species pairs, providing a natural origin for the multistability of the full community. In contrast with the common association between bistability and antagonism, experiments reveal many positive interactions within and between community members. We find that multiple species display cooperative growth, and modeling predicts that this could drive the observed multistability within the community as well as non-canonical pairwise outcomes. A biochemical screening reveals that glutamate either reduces or eliminates cooperativity in the growth of several species, and we confirm that such supplementation reduces the extent of bistability across pairs and reduces multistability in the full community. Our findings provide a mechanistic explanation of how cooperative growth rather than competitive interactions can underlie multistability in microbial communities.

Multi-cell-line learning for the data-driven construction of mechanistic metabolic models.

Mammalian cells are commonly used as hosts in cell culture for biologics production in the pharmaceutical industry. Structured mechanistic models of metabolism have been used to capture complex cellular mechanisms that contribute to varying metabolic shifts in different cell lines. However, little research has focused on the impact of temporal changes in enzyme abundance and activity on the modeling of cell metabolism. In this work, we present a framework for constructing mechanistic models of metabolism that integrate growth-signaling control of enzyme activity and transcript dynamics. The proposed approach is applied to build models for three Chinese hamster ovary (CHO) cell lines using fed-batch culture data and time-series transcript profiles. Leveraging information from the transcriptome data, we develop a parameter estimation approach based on multi-cell-line (MCL) learning, which combines data sets from different cell lines and trains the individual cell-line models jointly to improve model accuracy. The computational results demonstrate the important role of growth signaling and transcript variability in metabolic models as well as the virtue of the MCL approach for constructing cell-line models with a limited amount of data. The resulting models exhibit a high level of accuracy in predicting distinct metabolic behaviors in the different cell lines; these models can potentially be used to accelerate the process and cell-line development for the biomanufacturing of new protein therapeutics.

Impact of High-Fat Diet and Exercise on Bone and Bile Acid Metabolism in Rats.

Bile acids help facilitate intestinal lipid absorption and have endocrine activity in glucose, lipid and bone metabolism. Obesity and exercise influence bile acid metabolism and have opposite effects in bone. This study investigates if regular exercise helps mitigate the adverse effects of obesity on bone, potentially by reversing alterations in bile acid metabolism. Four-month-old female Sprague Dawley rats either received a high-fat diet (HFD) or a chow-based standard diet (lean controls). During the 10-month study period, half of the animals performed 30 min of running at moderate speed on five consecutive days followed by two days of rest. The other half was kept inactive (inactive controls). At the study's end, bone quality was assessed by microcomputed tomography and biomechanical testing. Bile acids were measured in serum and stool. HFD feeding was related to reduced trabecular (-33%, p = 1.14 × 10-7) and cortical (-21%, p = 2.9 × 10-8) bone mass and lowered femoral stiffness (12-41%, p = 0.005). Furthermore, the HFD decreased total bile acids in serum (-37%, p = 1.0 × 10-6) but increased bile acids in stool (+2-fold, p = 7.3 × 10-9). These quantitative effects were accompanied by changes in the relative abundance of individual bile acids. The concentration of serum bile acids correlated positively with all cortical bone parameters (r = 0.593-0.708), whilst stool levels showed inverse correlations at the cortical (r = -0.651--0.805) and trabecular level (r = -0.656--0.750). Exercise improved some trabecular and cortical bone quality parameters (+11-31%, p = 0.043 to 0.001) in lean controls but failed to revert the bone loss related to the HFD. Similarly, changes in bile acid metabolism were not mitigated by exercise. Prolonged HFD consumption induced quantitative and qualitative alterations in bile acid metabolism, accompanied by bone loss. Tight correlations between bile acids and structural indices of bone quality support further functional analyses on the potential role of bile acids in bone metabolism. Regular moderate exercise improved trabecular and cortical bone quality in lean controls but failed in mitigating the effects related to the HFD in bone and bile acid metabolism.

Heat stress has divergent effects on the milk microbiota of Holstein and Brown Swiss cows.

Heat stress (HS) is one of the pivotal causes of economic losses in dairy industries and affects welfare and performance, but its effect on milk microbiota remains elusive. It is also unclear if and how different breeds may cope with HS in sustaining productive performance. The objectives of this study were to compare a) the performance of 2 dairy breeds, namely Holstein and Brown Swiss, subjected to HS and b) the different effects of HS on the milk microbiota of the 2 breeds in thermal comfort conditions and HS. The study was carried out on 36 dairy cows, 18 per breed. The HS was induced by switching off the cooling system during a natural heat wave for 4 d. Besides the Temperature Humidity Index (THI), the animal stress was confirmed by measuring respiratory frequency and rectal temperature twice daily at 4 a.m. and 3 p.m. The HS differently impacted the 2 breeds. Rectal temperatures were higher in Holstein cows, while no changes in rectal temperature were found in Brown Swiss. Milk yield recording and sampling were performed during the morning milking of d 1 (at 4.00 a.m.) and afternoon milking of d 4 (at 5.00 p.m.). Productive parameters were also different: milk yield, fat-corrected milk, energy-corrected milk, protein and casein content, and renneting parameters were decreased in Holstein but remained unaffected in Brown Swiss. The HS also modified the milk microbiota of the 2 breeds differently. During HS, the Brown Swiss milk microbiota was richer (α diversity) than the Holstein one. Comparing the time points before and during HS within breeds showed that Brown Swiss milk microbiota was less affected by HS than Holstein's. Under the same thermal comfort condition, milk microbiota did not discriminate between Brown Swiss and Holstein. Consistently with α and β diversity, the number of operational taxonomic units (OTUs) at the genus level that changed their abundance during HS was higher in Holstein (74 OTUs) than in Brown Swiss (only 20 OTUs). The most significant changes in abundance affected Acinetobacter, Chryseobacterium, Cutibacterium, Enterococcus, Lactococcus, Prevotella-9, Serratia, and Streptococcus. In conclusion, the present report confirms and extends previous studies by demonstrating that Brown Swiss cows regulate their body temperature better than the Holstein breed. The relative thermal tolerance to HS compared with Holstein is also confirmed by changes in milk uncultured microbiota, which were more evident in Holstein than in Brown Swiss.

Unlocking the therapeutic potential of Huoxiang Zhengqi San in cold and high humidity-induced diarrhea: Insights into intestinal microbiota modulation and digestive enzyme activity

Huoxiang Zhengqi San (HXZQS), a traditional Chinese herbal formula, enjoys widespread use in Chinese medicine to treat diarrhea with cold-dampness trapped spleen syndrome (CDSS), which is induced by exposure to cold and high humidity stress. This study aimed to explore its therapeutic mechanisms in mice, particularly focusing on the intestinal microbiota. Forty male SPF-grade KM mice were allocated into two groups: the normal control group (H-Cc, n = 10) and the CDSS group (H-Mc, n = 30). After modeling, H-Mc was subdivided into H-Mc (n = 15) and HXZQS treatment (H–Tc, n = 15) groups. Intestinal samples were analyzed for enzyme activity and microbiota composition. Our findings demonstrated a notable reduction in intestinal lactase activity post-HXZQS treatment (P < 0.05). Lactobacillus johnsonii, Lactobacillus reuteri, and Lactobacillus murinus emerged as the main dominant species across most groups. However, in the H-Mc group, Clostridium sensu stricto 1 was identified as the exclusive dominant bacteria. LEfSe analysis highlighted Clostridiales vadinBB60 group and Corynebacterium as differential bacteria in the H–Tc group, and Cyanobacteria unidentified specie in the H-Mc group. Predicted microbiota functions aligned with changes in abundance, notably in cofactors and vitamins metabolism. The collinear results of the intestinal microbiota interaction network showed that HXZQS restored cooperative interactions among rare bacteria by mitigating their mutual promotion. The HXZQS decoction effectively alleviates diarrhea with CDSS by regulating intestinal microbiota, digestive enzyme activity, and microbiota interaction. Notably, it enhances Clostridium vadinBB60 and suppresses Cyanobacteria unidentified specie, warranting further study.

Decadal trends and dynamics in the abundance and biomass of marine branchiopods in the southern part of the North Sea

Time-series are fundamental for enhancing our comprehension of plankton community dynamics and forecasting future changes that could significantly affect entire marine food chains and ecosystems. In this study, we investigated spatial and temporal variations in occurrence, abundance and body size of marine branchiopods in the Belgian Part of the North Sea (BPNS), using both traditional microscopy, as well as digital imaging (ZooSCAN). We studied the population dynamics of branchiopods collected between 2014 and 2021 in the BPNS and compared these results with a previously collected (2009–2010) dataset for the same area. The time series showed no significant changes in abundance (Podon spp., Evadne nordmanni) over the years, but we did observe a pronounced seasonal pattern, with both species completely absent in the winter months. Abundance and biomass were positively correlated with water temperature but negatively correlated with nutrient concentrations and turbidity. Additionally, Podon spp. abundance was negatively correlated with anthropogenic chemicals (i.e., polycyclic aromatic hydrocarbons). We employed generalized additive models to quantify the relative contribution of temperature, salinity, turbidity, chlorophyll a concentration and pollutant levels to the dynamics of the studied taxa. Turbidity and chlorophyll a concentrations were revealed to be the predictor with the highest importance in all models predicting the abundances/body size of the selected species. Anthropogenic chemicals were not informative in explaining branchiopod abundance or body size. The findings of this study establish a baseline for future studies, which is essential for our understanding of the zooplankton dynamics in the North Sea, particularly in the context of climate change and changing water quality.

Effect of the DASH diet on the sodium-chloride cotransporter and aquaporin-2 in urinary extracellular vesicles.

The dietary approach to stop hypertension (DASH) diet combines the antihypertensive effect of a low sodium and high potassium diet. In particular, the potassium component of the diet acts as a switch in the distal convoluted tubule to reduce sodium reabsorption, similar to a diuretic but without the side effects. Previous trials to understand the mechanism of the DASH diet were based on animal models and did not characterize changes in human ion channel protein abundance. More recently, protein cargo of urinary extracellular vesicles (uEVs) has been shown to mirror tissue content and physiological changes within the kidney. We designed an inpatient open label nutritional study transitioning hypertensive volunteers from an American style diet to DASH diet to examine physiological changes in adults with stage 1 hypertension otherwise untreated (Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER 3rd, Simons-Morton DG, Karanja N, Lin PH; DASH-Sodium Collaborative Research Group. N Engl J Med 344: 3-10, 2001). Urine samples from this study were used for proteomic characterization of a large range of pure uEVs (small to large) to reveal kidney epithelium changes in response to the DASH diet. These samples were collected from nine volunteers at three time points, and mass spectrometry identified 1,800 proteins from all 27 samples. We demonstrated an increase in total SLC12A3 [sodium-chloride cotransporter (NCC)] abundance and a decrease in aquaporin-2 (AQP2) in uEVs with this mass spectrometry analysis, immunoblotting revealed a significant increase in the proportion of activated (phosphorylated) NCC to total NCC and a decrease in AQP2 from day 5 to day 11. This data demonstrates that the human kidney's response to nutritional interventions may be captured noninvasively by uEV protein abundance changes. Future studies need to confirm these findings in a larger cohort and focus on which factor drove the changes in NCC and AQP2, to which degree NCC and AQP2 contributed to the antihypertensive effect and address if some uEVs function also as a waste pathway for functionally inactive proteins rather than mirroring protein changes.NEW & NOTEWORTHY Numerous studies link DASH diet to lower blood pressure, but its mechanism is unclear. Urinary extracellular vesicles (uEVs) offer noninvasive insights, potentially replacing tissue sampling. Transitioning to DASH diet alters kidney transporters in our stage 1 hypertension cohort: AQP2 decreases, NCC increases in uEVs. This aligns with increased urine volume, reduced sodium reabsorption, and blood pressure decline. Our data highlight uEV protein changes as diet markers, suggesting some uEVs may function as waste pathways. We analyzed larger EVs alongside small EVs, and NCC in immunoblots across its molecular weight range.

Loss of Sunda clouded leopards and forest integrity drive potential impacts of mesopredator release on vulnerable avifauna

Amongst the unintended consequences of anthropogenic landscape conversion is declining apex predator abundance linked to loss of forest integrity, which can potentially re-order trophic networks. One such re-ordering, known as mesopredator release, occurs when medium-sized predators, also called mesopredators, rapidly increase in abundance following the decline in apex predator abundance, consequently reducing the abundance of mesopredator prey, notably including terrestrial avifauna. We examine the cascading impacts of declining Sunda clouded leopard abundance, itself consequent upon a reduction in forest integrity, on the mesopredator community of Sabah, Malaysia, to determine whether the phenomenon of mesopredator release is manifest and specifically whether it impacts the terrestrial avifauna community of pheasants and pittas. To explore this trophic interaction, we used a piecewise structural equation model to compare changes in the relative abundance of organisms. Our results suggest that loss of forest integrity may have broad impacts on the community and trigger mesopredator release, the two acting additively in their impact on already vulnerable species of terrestrial avifauna: a result not previously documented in tropical systems and rarely detected even on a global scale. The limiting effect that the Sunda clouded leopard has on the Sunda leopard cat could illuminate the mechanism whereby mesopredator release impacts this system. Both Bulwer's pheasant and pittas appear to be significantly impacted by the increase in Sunda leopard cats, while the great argus pheasant shows similar compelling, although not statistically significant, declines as Sunda leopard cats increase. The inverse relationship between Sunda clouded leopards and Sunda leopard cats suggests that if a mesopredator release exists it could have downstream consequences for some terrestrial avifauna. These results suggest the under-studied interface between mammalian carnivores and avifauna, or more broadly species interactions in general, could offer important conservation tool for holistic ecosystem conservation efforts.

Prospective evaluation of the breast microbiome and tumor microenvironment-related biomarkers of response to neoadjuvant systemic therapy in triple negative breast cancer.

TPS615 Background: Predictive biomarkers of response to combination chemotherapy and immune-checkpoint inhibitors are urgently needed to tailor treatment recommendations for patients with early-stage triple negative breast cancer (eTNBC). Our group has demonstrated that tumour-associated microbiota in primary breast tumours represent promising and novel candidate biomarkers for patients with breast cancer. We aim to prospectively interrogate the breast cancer microbiome and tumour microenvironment (TME) of eTNBC treated with neoadjuvant chemo-immunotherapy, and correlate with clinical outcome. Methods: Trial design: This prospective translational biomarker study is enrolling patients with eTNBC suitable for standard neoadjuvant systemic therapy followed by definitive surgery. The primary objective is to evaluate the change in breast cancer microbiome composition pre- and post-therapy. Secondary objectives include correlation of the breast microbiome with pathologic complete response (pCR) and survival outcomes, tumor infiltrating lymphocytes (TILs), PDL-1 and immune subset analysis, extracellular vesicles analysis and analysis of gut microbiome. Tumor tissue samples will be collected at baseline (mandatory research biopsy) and at the time of surgery. Microbiome evaluation will be conducted using metagenomic sequencing to assess changes in the relative abundance of microbial taxa. Blood and stool samples will be collected and analysed at baseline, on-treatment, at the time of surgery and post-operatively for secondary endpoints. Statistical analysis: Hierarchical clustering of samples based on relative abundance of the operational taxonomic units (OTUs) with sample composition at family and genus level will be performed. Alpha Diversity (Shannon Diversity Index) and Beta Diversity (Jaccard Similarity Index) will be analysed. Principal component analysis (PCA) and Random Forest analysis will be performed for classification and clustering analysis. Comparison of taxa or functions between clinical cohorts will be performed (two tailed Z test) and corrected using the false discovery rate to determine Q-values. Thirty patients will be recruited over 18-24 months. Current status: This University College Cork sponsored trial received ethics approval from the CREC in January 2024 and recruitment is ongoing. Those interested can contact uccctg@ucc.ie. This trial will provide a deeper insight into the potential role of the local breast microbiome as a predictive biomarker for response to neoadjuvant therapy in patients with eTNBC. The results will guide further studies exploring optimal immunomodulatory combinations for the treatment of TNBC and may provide evidence regarding future therapeutic targeting of the breast cancer microbiome.

The relationship of sphingolipid mechanisms with oxidative stress and changes in mitochondria during functional unloading of postural muscles

Background. Prolonged inactivity of skeletal muscles is accompanied by the development of oxidative stress and changes in sphingolipid metabolism. The relationship of sphingolipid mechanisms with generation of reactive oxygen species (ROS) in muscles subjected to functional unloading has not been studied.The aim. To identify the relationship between changes in sphingomyelinase and ceramide abundance and ROS production in rat soleus muscle during functional unloading.Methods. Male Wistar rats were subjected to hindlimb suspension for 12 hours or 14 days with the acid sphingomyelinase (ASM) inhibitor amitriptyline (AMI). The levels of ASM, ceramide and ROS were determined by fluorescence microscopy on histological sections. Pro-oxidant enzymes (NADPH oxidases 2 and 4 (NOX2 and NOX4)), cytochrome c oxidase (COX IV), the regulator of mitochondrial biogenesis PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) in muscle homogenates were studied by Western blotting, which also was used for assessment of ceramide and ASM in the isolated mitochondrial fraction. The effects of sphingomyelinase and prooxidants on ceramide, ASM, ROS and NOX2 levels were studied in an ex vivo model by incubating the muscle with exogenous sphingomyelinase or H2O2.Results. 12-hour hindlimb suspension was accompanied by an increase in the level of ASM and ceramide in rat soleus muscle. Unloading for 14 days was characterized by an increase in ASM, ceramide, ROS, NOX2, NOX4 and a decrease in COX IV and PGC-1α levels. ASM and ceramide were also increased in the mitochondrial fraction of muscle. The ASM inhibitor amitriptyline partially or completely prevented the changes caused by the unloading. In the ex vivo model, the stimulating effect of exogenous sphingomyelinase on the ROS and NOX2 levels in rat soleus muscle was found, whereas H2O2 stimulated muscle ASM and ceramide production.Conclusion. A close relationship has been established between the sphingomyeli-nase pathway of ceramide formation and ROS production in skeletal muscle under conditions of functional unloading.

Microbiome origin and stress-related changes in bacterial abundance of the photosymbiotic sea slug Berghia stephanieae (Á. Valdés, 2005)

The precise mechanisms that allow animals and phototrophic organisms to form a stable photosymbiotic relationship are still unknown. While previous studies focused on genomic adaptations of the animal host, more recent research looked into the role of bacteria in photosymbiosis. Here, we analyzed the core microbiome of the sea slug Berghia stephanieae and its food source Exaiptasia diaphana to understand if the microbiome and the linked bacterial metabolic pathways differ between unstable and stable photosymbiosis. This sea slug feeds solely on the model cnidarian E. diaphana and steals their photobionts which the slug can only maintain for a week. We additionally examined the influence of light and starvation stress on the slug’s bacterial composition, which are common experimental set-ups to elucidate the photosymbiotic relationship in the slugs. Our results show that the core microbiome of B. stephanieae and E. diaphana differed significantly suggesting that the slug’s microbiome is not obtained from its food source or the water column and indicates a vertical transmission. Further, differences in metabolic pathways imply that the microbiome of B. stephanieae does not support a stable photosymbiosis due to an insufficient nitrogen cycle on part of the photobiont. Starving the slugs induced a shift towards an increased abundance of potential pathogens and led to a downregulation in the sulphur cycle. Yet, starvation in darkness resulted in the depletion of most bacteria and induced a metabolic switch toward bacterial nitrogen fixation. This emphasizes that different holobiont members contribute to essential nutrient cycles, and it is important to look beyond the photobiont to understand the sea slug holobiont.

Bumble bee responses to climate and landscapes: Investigating habitat associations and species assemblages across geographic regions in the United States of America.

Bumble bees are integral pollinators of native and cultivated plant communities, but species are undergoing significant changes in range and abundance on a global scale. Climate change and land cover alteration are key drivers in pollinator declines; however, limited research has evaluated the cumulative effects of these factors on bumble bee assemblages. This study tests bumble bee assemblage (calculated as richness and abundance) responses to climate and land use by modeling species-specific habitat requirements, and assemblage-level responses across geographic regions. We integrated species richness, abundance, and distribution data for 18 bumble bee species with site-specific bioclimatic, landscape composition, and landscape configuration data to evaluate the effects of multiple environmental stressors on bumble bee assemblages throughout 433 agricultural fields in Florida, Indiana, Kansas, Kentucky, Maryland, South Carolina, Utah, Virginia, and West Virginia from 2018 to 2020. Distinct east versus west groupings emerged when evaluating species-specific habitat associations, prompting a detailed evaluation of bumble bee assemblages by geographic region. Maximum temperature of warmest month and precipitation of driest month had a positive impact on bumble bee assemblages in the Corn Belt/Appalachian/northeast, southeast, and northern plains regions, but a negative impact on the mountain region. Further, forest land cover surrounding agricultural fields was highlighted as supporting more rich and abundant bumble bee assemblages. Overall, climate and land use combine to drive bumble bee assemblages, but how those processes operate is idiosyncratic and spatially contingent across regions. From these findings, we suggested regionally specific management practices to best support rich and abundant bumble bee assemblages in agroecosystems. Results from this study contribute to a better understanding of climate and landscape factors affecting bumble bees and their habitats throughout the United States.

The Role of Insulin-like Growth Factor Binding Protein (IGFBP)-2 in DNA Repair and Chemoresistance in Breast Cancer Cells.

The role if insulin-like growth factor binding protein-2 (IGFBP-2) in mediating chemoresistance in breast cancer cells has been demonstrated, but the mechanism of action is unclear. This study aimed to further investigate the role of IGFBP-2 in the DNA damage response induced by etoposide in MCF-7, T47D (ER+ve), and MDA-MB-231 (ER-ve) breast cancer cell lines. In the presence or absence of etoposide, IGFBP-2 was silenced using siRNA in the ER-positive cell lines, or exogenous IGFBP-2 was added to the ER-negative MDA-MB-231 cells. Cell number and death were assessed using trypan blue dye exclusion assay, changes in abundance of proteins were monitored using Western blotting of whole cell lysates, and localization and abundance were determined using immunofluorescence and cell fractionation. Results from ER-positive cell lines demonstrated that upon exposure to etoposide, loss of IGFBP-2 enhanced cell death, and this was associated with a reduction in P-DNA-PKcs and an increase in γH2AX. Conversely, with ER-negative cells, the addition of IGFBP-2 in the presence of etoposide resulted in cell survival, an increase in P-DNA-PKcs, and a reduction in γH2AX. In summary, IGFBP-2 is a survival factor for breast cancer cells that is associated with enhancement of the DNA repair mechanism.

Sediment dynamics and geomorphology in coastal areas affect long-term abundance of waders

Millions of migrating and wintering waders depend on coastal areas and estuaries for feeding and to replenish body reserves. These habitats are dynamic, with changing intertidal flats and sediments due to natural and climate-driven processes. The aims of this study were to examine whether physical conditions of intertidal flats such as geomorphology and sediment compositions could explain abundance of wader species, and furthermore whether changes in these conditions over time influenced changes in abundance of waders. In addition to physical structures such as datum (level), slope and sediment composition of intertidal flats, dynamic variables connected to tidal cycles such as distance of the waterline from the coast and duration of water cover were included. Penetration of the sea floor was measured as a proxy for sediment composition. The study was conducted in the Danish section of the Wadden Sea during 1981–1986 and 2008–2009 with additional data from 2020. The focus was on 12 widespread wader species. PCA analysis revealed that wader species were distributed in relation to tidal cycles such as duration of water cover and the position of waterline and to the physical structures, datum, slope and penetration, in decreasing order. With regard to the physical structures, pairwise comparisons of distribution of waders species showed that mean datum (level) was significantly different for 51 pairs of species out of 66 comparisons, mean penetration values differed for 34 pairs, and mean slope differed for 26 pairs of wader species. Long-term changes of physical structures of transects revealed that changes of densities of 10 wader species were significantly correlated with changes per year in one or more of the physical structures: seven wader species were significantly correlated with changes per year of mean datum (level) of transects (Lapwing was positively correlated while Avocet, Golden Plover, Grey Plover, Dunlin, Bar-tailed Godwit and Redshank were negatively correlated), five species with mean slope (Oystercatcher, Ringed Plover and Knut were positively correlated and Grey Plover and Redshank were negatively correlated), and three species with mean penetration values (sediment composition) of transects (Avocet and Bar-tailed Godwit were positively correlated and Lapwing was negatively correlated). The study shows that long-term changes of physical structures of intertidal flats affected abundance of wader species. The results are important for interpretation effects of erosion and accretion of coastal areas as consequences of natural and climate driven processes such as sea level rise and coastal squeeze.

Chemotherapy-induced gut microbiome disruption, inflammation, and cognitive decline in female patients with breast cancer

Chemotherapy is notorious for causing behavioral side effects (e.g., cognitive decline). Notably, the gut microbiome has recently been reported to communicate with the brain to affect behavior, including cognition. Thus, the aim of this clinical longitudinal observational study was to determine whether chemotherapy-induced disruption of the gut microbial community structure relates to cognitive decline and circulating inflammatory signals. Fecal samples, blood, and cognitive measures were collected from 77 patients with breast cancer before, during, and after chemotherapy. Chemotherapy altered the gut microbiome community structure and increased circulating TNF-α. Both the chemotherapy-induced changes in microbial relative abundance and decreased microbial diversity were related to elevated circulating pro-inflammatory cytokines TNF-α and IL-6. Participants reported subjective cognitive decline during chemotherapy, which was not related to changes in the gut microbiome or inflammatory markers. In contrast, a decrease in overall objective cognition was related to a decrease in microbial diversity, independent of circulating cytokines. Stratification of subjects, via a reliable change index based on 4 objective cognitive tests, identified objective cognitive decline in 35% of the subjects. Based on a differential microbial abundance analysis, those characterized by cognitive decline had unique taxonomic shifts (Faecalibacterium, Bacteroides, Fusicatenibacter, Erysipelotrichaceae UCG-003, and Subdoligranulum) over chemotherapy treatment compared to those without cognitive decline. Taken together, gut microbiome change was associated with cognitive decline during chemotherapy, independent of chemotherapy-induced inflammation. These results suggest that microbiome-related strategies may be useful for predicting and preventing behavioral side effects of chemotherapy.

Seasonal dynamics of antibiotic resistance genes and mobile genetic elements in a subtropical coastal ecosystem: Implications for environmental health risks

Antibiotic resistance poses a considerable global public health concern, leading to heightened rates of illness and mortality. However, the impact of seasonal variations and environmental factors on the health risks associated with antibiotic resistance genes (ARGs) and their assembly mechanisms is not fully understood. Based on metagenomic sequencing, this study investigated the antibiotic resistome, mobile genetic elements (MGEs), and microbiomes in a subtropical coastal ecosystem of the Beibu Gulf, China, over autumn and winter, and explored the factors influencing seasonal changes in ARG and MGE abundance and diversity. Results indicated that ARG abundance and diversity were higher in winter than in autumn, with beta-lactam and multidrug resistance genes being the most diverse and abundant, respectively. Similarly, MGE abundance and diversity increased in winter and were strongly correlated with ARGs. In contrast, more pronounced associations between microbial communities, especially archaea, and the antibiotic resistome were observed in autumn than in winter. The co-occurrence network identified multiple interactions between MGEs and various multidrug efflux pumps in winter, suggesting a potential for ARG dissemination. Multivariate correlation analyses and path modeling indicated that environmental factors driving microbial community changes predominantly influenced antibiotic resistome assembly in autumn, while the relative importance of MGEs increased significantly in winter. These findings suggest an elevated health risk associated with antimicrobial resistance in the Beibu Gulf during winter, attributed to the dissemination of ARGs by horizontal gene transfer. The observed seasonal variations highlight the dynamic nature of antibiotic resistance dissemination in coastal ecosystems, emphasizing the need for comprehensive surveillance and management measures to address the growing threat of antimicrobial resistance in vulnerable environments.

The sources and physical–chemical conditions of gold mineralization in the Qi189 porphyry deposit, Qiyugou gold orefield, Eastern Qinling

The Qiyugou gold orefield is situated in the Eastern Qinling. It is a magmatic hydrothermal system, which includes cryptoexplosive breccia-type, vein-type, and porphyry gold deposits. However, the gold sources and physical–chemical conditions of precipitation of the newly discovered porphyry gold deposit, the Qi189, have not yet been well studied. It also hinders the comprehensive understanding of magmatic–hydrothermal gold systems in the Qiyugou gold orefield. Thus, detailed field and microscopic observations, C–O–He–Ar isotopic analysis, in situ major/trace element analysis, and thermodynamic studies on the Qi189 porphyry gold deposit have been carried out in this study. This deposit has three hydrothermal stages: the (I) early quartz–K-feldspar–molybdenite–magnetite stage, (II) middle quartz–sericite–pyrite–Te–Bi-mineral stage, as well as (III) late calcite–quartz stage. The carbon and He–Ar isotopic compositions suggest deep-seated sources of ore-forming fluids with mantle component proportions of up to 37 %. Oxygen isotopic compositions indicate the gradual involvement of more meteoric water in ore-forming fluids during stages I–III. The meteoric water input and reduction in temperature and pressure in the early stage II increased oxygen fugacity and decreased the pH values of ore-forming fluids. Then, in hematite and sulfides formation during late stage II, the oxygen and sulfur fugacities of ore-forming fluids gradually decreased. Precipitation of native gold and Au-bearing telluride grains with quartz-sericite alteration in stage II is significant for Au enrichment, which occurred under acidic (pH = 3.64–5.71), low-logfO2 (<-34.86), low-logfS2 (−13.07 to −11.13) and low-logfTe2 (−15.55 to −10.32) conditions. Therefore, abundant mantle components and changes in the pH, logfO2, logfS2, and logfTe2 of the ore-forming fluids play important roles in gold enrichment. Combined with previous studies, this work also provides some new evidence for identifying a magmatic-hydrothermal gold system in this district, including similar sulfide trace elements, δ13CV-PDB compositions, and changes in logfO2 and logfS2 of various types of gold deposits in a gold orefield.