Loss of the NF-κB negative regulator Pirk in Drosophila links brain and gut immunity to neurodegeneration

A gut–brain axis influenced by host innate immunity and resident microbiota has been implicated in neurological conditions including Alzheimer’s disease. However, the precise connection of innate immunity to Alzheimer’s disease remains unclear. Using Pirk, a negative regulator of the IMD/NF-κB pathway in Drosophila, we studied the neurological phenotypes induced when genetically predisposing flies to chronically over-active immunity. Pirk mutants exhibited age-dependent neurological phenotypes such as reduced locomotion and altered sleep patterns coupled to an increased number of brain lesions. Gut-specific pirk-RNA interference led to earlier onset of the neurological phenotypes which, alongside changes in intestinal bacteria in pirk mutants, highlighted a potential early role for the intestinal ecosystem in the onset of neurodegeneration. In contrast, glia-specific RNA interference of pirk resulted in late onset of the relevant phenotypes suggesting a later contribution of the nervous system to the underlying neuropathology. Knockout of the antimicrobial peptide (AMP) gene AttacinD or rearing flies in axenic conditions recovered some of the neurological phenotypes, suggesting both chronic AMP gene expression as well as gut bacteria changes as mediators. Our results indicate an evolutionarily conserved path to neurodegeneration linked to dysregulated immunity. They also reveal that in this context, age-dependent neurodegeneration can happen in less complex non-vertebrate brains in the absence of beta-amyloid or tau aggregation

Alcohol-induced gut permeability defect through dysbiosis and enterocytic mitochondrial interference causing pro-inflammatory macrophages in a dose dependent manner

Although toxicity of alcohol toward the intestines and immunity is mentioned, there might be different effect of alcohol in a low and a high dose and the rodent model development using a simple SHIRPA binary score night be useful. Hence, a low and high dose of alcohol (6.30 and 1.26 g/kg/day) were administered in might for 16 weeks before determination of several parameters. As such, the peak blood alcohol concentration (BAC) of low and high dose of alcohol were approximately at 0.05 and 0.15%, respectively, at 1 h post-administration, which correlated with SHIRPA score at 1.8 ± 0.8 and 7.2 ± 0.6, respectively. After 16 wk of administration, a significant liver injury in high-dose alcohol was indicated by liver enzymes, liver weight, histology score, apoptosis, and hepatic accumulation of triglyceride (TG) and oxidative stress (malondialdehyde; MDA) with reduced anti-oxidant (glutathione). Meanwhile, low-dose alcohol demonstrated only elevated apoptosis with increased TG and MDA in liver tissue. Leaky gut from both dose of alcohol was also demonstrated by FITC-dextran, endotoxemia, serum beta glucan, and reduced occludin. However, bacterial abundance (microbiome analysis) of the feces from small bowel of high-dose alcohol, but not the low dose, was different from the control (increased Alitipes spp. with reduced Lachnospiraceae). In conclusion, both low- and high-dose alcohol induced leaky gut, while only the high-dose caused gut dysbiosis and alcohol damaged mitochondria but enhanced glycolysis in enterocytes and macrophages. Leaky gut might be more sensitive than dysbiosis to determine alcohol-induced intestinal injury

Long-term exposure to fine particulate matter interacting with individual conditions increase breast cancer incidence: a large-scale Chinese cohort

Background: Breast cancer is the most frequently diagnosed malignancy among women worldwide. This study aimed to investigate the impact of long-term fine particulate matter (PM2.5) exposure on breast cancer incidence in a cohort of 281,152 women from the China Kadoorie Biobank who were initially free of breast cancer. Results: PM2.5 concentrations were estimated using a high-resolution satellite-based model, and breast cancer cases were ascertained through national databases. Over a median follow-up of 11.12 years, 2393 new breast cancer cases were reported. Analyses using Cox proportional hazard and restricted cubic spline models demonstrated a non-linear association between PM2.5 exposure and breast cancer incidence, with a marked increase in risk observed once PM2.5surpassed 53.6 μg/m3. For every 10 μg/m3 increase in PM2.5, the hazard ratio for breast cancer incidence was 1.07 (95% confidence interval: 1.03–1.12). Furthermore, interactions were noted between PM2.5, physical activity, and life satisfaction, indicating that high pollution levels may diminish the protective benefits of exercise and positive psychological well-being. Conclusions: These findings highlight the need for stringent air pollution control measures and underscore the importance of integrated strategies that consider environmental, lifestyle, and psychological factors to reduce the burden of breast cancer

Immersion patterns alone can predict vessel following by albatrosses

Many pelagic seabird species are threatened by bycatch in fisheries. Bycatch risk assessments benefit from quantifying the frequency, duration, and location of individual seabird interactions with fishing vessels. However, proximity-based interaction analyses are limited by the availability and spatiotemporal resolution of bird and vessel tracking data. Here, we examined whether patterns in seabird landing and take-off behaviour (immersion) derived from GLS-immersion loggers (0.167 Hz) can detect vessel interactions when tracking data are lacking or incomplete. We identified closeproximity seabird-vessel interactions by spatiotemporally matching high-resolution GPS data (0.02-1 Hz) from 45 black-browed albatrosses (Thalassarche melanophris) to Automatic Identification System (AIS) data from trawler vessels. We used random forest models to investigate whether immersion patterns alone could distinguish these vessel interactions from natural foraging behaviours. We observed multiple seabird-vessel interaction types, with active vessel “following” (with multiple landings) comprising only 59% of discrete interaction events. Other interaction types included “stopping” (with 1 landing) and “passing” (with 0 landings). Using immersion patterns alone, we could distinguish vessel following in >80% of both foraging timesteps and discrete foraging bouts, with false positive vessel following detections totalling <10% of true positives. We found that GLS-immersion loggers sometimes remain wet following take-off, leading to inflated durations of on-water periods. However, leaving this error uncorrected only slightly reduced the performance of our random forest models. Policy implications. We demonstrate that seabird immersion patterns alone can detect high-risk seabird-vessel interactions, even in the absence of locational data for both seabirds and vessels. Our approach could allow for more comprehensive seabird bycatch risk assessments that quantify previously hidden seabird-vessel interactions, such as those involving migratory life history stages and illegal, unreported, or unregulated (IUU) fishing vessels

Cephalhaematoma in Sweden, a Population‐Based Register Study

Aim: The primary aim was to investigate the incidence, birth characteristics, and timing of diagnosis of cephalhaematoma (CH). The secondary aim was to explore associations between CH and complications during the neonatal period and infancy. Methods: This is a nationwide population‐based register study of infants (< 12 months) born in Sweden from 1997 to 2018. Information was retrieved from health registers of the Swedish National Board of Health and Welfare. Cases were infants with a diagnosis of birth‐related CH. Results: The study comprises 2930 infants with CH. The incidence was 2.2 per 1000 births and increased during the study period. Most CH cases had a spontaneous vaginal delivery. Risk factors were ventouse, born preterm, large‐for‐gestational age, and occiput posterior presentation. Two‐thirds were diagnosed before 7 days of life. A delayed diagnosis during later infancy became more common from the year 2000. Newborn infants had an increased risk of jaundice (10%). CH was associated with hypoxic encephalopathy (2.5%), convulsions (3.5%), skull fractures (0.6%), intraventricular haemorrhage (0.2%), subdural haemorrhage (0.5%) and stroke (0.2%). Conclusion: A substantial number of CH cases had a delayed diagnosis. A minority displayed symptoms of serious head trauma. CH was associated with intracranial haemorrhage

Integrating TSPO-PET imaging with metabolomics for enhanced prognostic accuracy in multiple sclerosis

Background: Predicting disease progression in multiple sclerosis (MS) remains challenging. PET imaging with 18 kDa translocator protein (TSPO) radioligands can detect microglial and astrocyte activation beyond MRI-visible lesions, which has been shown to be highly predictive of disease progression. We previously demonstrated that nuclear magnetic resonance (NMR)-based metabolomics could accurately distinguish between relapsing-remitting (RRMS) and secondary progressive MS (SPMS). This study investigates whether combining TSPO imaging with metabolomics enhances predictive accuracy in a similar setting. Methods: Blood samples were collected from 87 MS patients undergoing PET imaging with the TSPO-binding radioligand 11C-PK11195 in Finland. Patient disability was assessed using the expanded disability status scale (EDSS) at baseline and 1 year later. Serum metabolomics was performed to identify biomarkers associated with TSPO binding and disease progression. Results: Greater TSPO availability in the normal-appearing white matter and perilesional regions correlated with higher EDSS. Serum metabolites glutamate (p=0.02), glutamine (p=0.006), and glucose (p=0.008), detected by NMR, effectively distinguished future progressors. These three metabolites alone predicted progression with the same accuracy as TSPO-PET imaging (AUC 0.78; p=0.0001), validated in an independent cohort. Combining serum metabolite data with PET imaging significantly improved predictive power, achieving an AUC of 0.98 (p<0.0001). Conclusion: Measuring three specific serum metabolites is as effective as TSPO imaging in predicting MS progression. However, integrating TSPO imaging with serum metabolite analysis substantially enhances predictive accuracy. Given the simplicity and affordability of NMR analysis, this approach could lead to more personalised, accessible treatment strategies and serve as a valuable tool for clinical trial stratification

A graph-theoretic framework for free-parafermion solvability

We present a graph-theoretic characterization of when a quantum spin model admits an exact solution via a mapping to free parafermions. Our characterization is based on the concept of a frustration graph, which represents the commutation relations between Weyl operators of a Hamiltonian. We show that a quantum spin system has an exact free-parafermion solution if its frustration graph is an oriented indifference graph. Furthermore, we show that if the frustration graph of a model can be dipath oriented via switching operations, then the model is integrable in the sense that there is a family of commuting independent set charges. Additionally, we establish an efficient algorithm for deciding whether this is possible. Our characterization extends that given for free-fermion solvability. Finally, we apply our results to solve three qudit spin models

Local mapping of the nanoscale viscoelastic properties of fluid membranes by AFM nanorheology

Biological membranes are intrinsically dynamic entities that continually adapt their biophysical properties and molecular organisation to support cellular function. Current microscopy techniques can derive high-resolution structural information of labelled molecules but quantifying the associated viscoelastic behaviour with nanometre precision remains challenging. Here, we develop an approach based on atomic force microscopy in conjunction with fast nano-actuators to map the viscoelastic response of unlabelled supported membranes with nanometre spatial resolution. On fluid membranes, we show that the method can quantify local variations in the molecular mobility of the lipids and derive a diffusion coefficient. We confirm our experimental approach with molecular dynamics simulations, also highlighting the role played by the water at the interface with the membrane on the measurement. Probing ternary model bilayers reveals spatial correlations in the local diffusion over distances of ≈20 nm within liquid disordered domains. This lateral correlation is enhanced in native bovine lens membranes, where the inclusion of protein-rich domains induces four-fold variations in the diffusion coefficient across < 100 nm of the fluid regions, consistent with biological function. Our findings suggest that diffusion is highly localised in fluid biomembranes

The multi-dimensional environmental impact of global crop commodities

Agriculture is one of the leading causes of detrimental environmental impacts, including greenhouse gas emissions, biodiversity loss and depletion of freshwater resources. Such impacts can be assessed by environmental sustainability indices; however, limitations in current indicators necessitate the development of more robust and standardized crop-specific environmental sustainability indices. Here we developed the crop environmental sustainability index (PLANTdex), a spatially explicit index (5 arcmin resolution) quantifying crop production’s environmental impacts. PLANTdex includes globally standardized indicators of environmental impacts assessing water stress and biodiversity loss via five emissions pathways: greenhouse gas emissions, water consumption, land occupation, and nitrogen and phosphorus fertilizer application. We applied PLANTdex to 16 crops, revealing high variability across production system efficiencies, crop types and local context environmental sensitivities. Globally and nationally, no clear correlation emerged between PLANTdex scores and crop production, but stronger correlations were evident at finer spatial scales and for individual crops. Sugar cane showed the strongest negative correlation (low impacts in high-production areas), while oil palm had the strongest positive correlation (high impacts in high-production areas), highlighting the importance of sub-national, crop-specific assessments. PLANTdex’s spatial resolution and crop specificity make it valuable for initiatives such as the Taskforce on Nature-related Financial Disclosures and corporate sustainability strategies

Leveraging Noncovalent Interactions for the Binding of CO by a Weakly Lewis Acidic Borane

Known boron carbonyl complexes either exploit very high Lewis acidity or a low oxidation state boron centre in order to capture CO. By contrast, we report a carbonyl complex featuring a simple tri‐coordinate borane, characterized by a Lewis acidity which is only marginally higher than B(NMe2)3. {(Ph2P)xanth}3B features a solid‐state structure in which two of the three B‐bound xanth(PPh2) units are projected above the BC3 plane, generating an up, up, down conformation. Quantum chemical methods, however, reveal that the alternative up, up, up alignment, characterized by a cage‐like geometry and enhanced intramolecular noncovalent interactions, is favored significantly in silico (by ca. 33.0 kcal mol−1). Although this conformation is optimal for binding polar C3‐symmetric H‐bond donors such as NH3 (and related guests such as H2O and MeNH2) the binding of essentially nonpolar substrates such as CO would be expected to be weak at best. However, exposure of {(Ph2P)xanth}3B to CO under mild conditions (1 bar, 25 °C) reversibly yields {(Ph2P)xanth}3B·CO, a tractable cage‐like borane carbonyl adduct featuring a central BCO moiety shrouded by xanth(PPh2) moieties. Dispersion forces are critical to substrate binding: the two binding modes in which the B‐bound CO guest is located inside/outside the host cage differ in energy by 59.5 kcal mol−1