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APOE4 and infectious diseases jointly contribute to brain glucose hypometabolism, a biomarker of Alzheimer’s pathology: New findings from the ADNI
Background Impaired brain glucose metabolism is a preclinical feature of neurodegenerative diseases such as Alzheimer’s disease (AD). Infections may promote AD-related pathology. Therefore, we investigated the interplay between infections and APOE4, a strong genetic risk factor for AD. Methods We analyzed data on 1,509 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database using multivariate linear regression models. The outcomes were rank-normalized hypometabolic convergence index (HCI), statistical regions of interest (SROI) for AD, and mild cognitive impairment (MCI). Marginal mean estimates for infections, stratified by APOE4 carrier status, were then computed. Results Prior infections were associated with greater HCI [β = 0.15, 95% CI: 0.03, 0.27, p = 0.01]. The combined effects of infections and APOE4 carriers on HCI levels were significantly greater than either variable alone. Among APOE4 carriers, the estimated marginal mean was 0.62, rising to 0.77, with infections (p<0.001), indicating an interaction effect. Carriers with multiple infections showed greater hypometabolism (higher HCI), with an estimate of 0.44 (p = 0.01) compared to 0.11 (p = 0.08) for those with a single infection, revealing a dose-response relationship. The estimates for the association of infections with SROI AD and SROI MCI were β = -0.01 (p = 0.02) and β = -0.01 (p = 0.04), respectively. Conclusion Our findings suggest that infections and APOE4 jointly contribute to brain glucose hypometabolism and AD pathology, supporting a “multi-hit” mechanism in AD development.
Patterns and implications of spatial covariation in herbivore functions on resilience of coral reefs
Abstract Persistent shifts to undesired ecological states, such as shifts from coral to macroalgae, are becoming more common. This highlights the need to understand processes that can help restore affected ecosystems. Herbivory on coral reefs is widely recognized as a key interaction that can keep macroalgae from outcompeting coral. Most attention has been on the role ‘grazing’ herbivores play in preventing the establishment of macroalgae, while less research has focused on the role of ‘browsers’ in extirpating macroalgae. Here we explored patterns, environmental correlates and state shift consequences of spatial co-variation in grazing and browsing functions of herbivorous fishes. Grazing and browsing rates were not highly correlated across 20 lagoon sites in Moorea, French Polynesia, but did cluster into 3 (of 4) combinations of high and low consumption rates (no site had low grazing but high browsing). Consumption rates were not correlated with grazer or browser fish biomass, but both were predicted by specific environmental variables. Experiments revealed that reversibility of a macroalgal state shift was strongly related to spatial variation in browsing intensity. Our findings provide insights and simple diagnostic tools regarding heterogeneity in top-down forcing that influences the vulnerability to and reversibility of shifts to macroalgae on coral reefs.
Topological confinement by a membrane anchor suppresses phase separation into protein aggregates: Implications for prion diseases
Protein misfolding and aggregation are a hallmark of various neurodegenerative disorders. However, the underlying mechanisms driving protein misfolding in the cellular context are incompletely understood. Here, we show that the two-dimensional confinement imposed by a membrane anchor stabilizes the native protein conformation and suppresses liquid–liquid phase separation (LLPS) and protein aggregation. Inherited prion diseases in humans and neurodegeneration in transgenic mice are linked to the expression of anchorless prion protein (PrP), suggesting that the C-terminal glycosylphosphatidylinositol (GPI) anchor of native PrP impedes spontaneous formation of neurotoxic and infectious PrP species. Combining unique in vitro and in vivo approaches, we demonstrate that anchoring to membranes prevents LLPS and spontaneous aggregation of PrP. Upon release from the membrane, PrP undergoes a conformational transition to detergent-insoluble aggregates. Our study demonstrates an essential role of the GPI anchor in preventing spontaneous misfolding of PrP C and provides a mechanistic basis for inherited prion diseases associated with anchorless PrP.
Deep learning-based differential gut flora for prediction of Parkinson’s
Background There had been extensive research on the role of the gut microbiota in human health and disease. Increasing evidence suggested that the gut-brain axis played a crucial role in Parkinson’s disease, with changes in the gut microbiota speculated to be involved in the pathogenesis of Parkinson’s disease or interfere with its treatment. However, studies utilizing deep learning methods to predict Parkinson’s disease through the gut microbiota were still limited. Therefore, the goal of this study was to develop an efficient and accurate prediction method based on deep learning by thoroughly analyzing gut microbiota data to achieve the diagnosis of Parkinson’s disease. Methods This study proposed a method for predicting Parkinson’s disease using differential gut microbiota, named the Parkinson Gut Prediction Method (PGPM). Initially, differential gut microbiota data were extracted from 39 Parkinson’s disease (PD) patients and their corresponding 39 healthy spouses. Subsequently, a preprocessing method called CRFS (combined ranking using random forest scores and principal component analysis contributions) was introduced for feature selection. Following this, the proposed LSIM (LSTM-penultimate to SVM Input Method) approach was utilized for classifying Parkinson’s patients. Finally, a soft voting mechanism was employed to predict Parkinson’s disease patients. Results The research results demonstrated that the Parkinson gut prediction method (PGPM), which utilized differential gut microbiota, performed excellently. The method achieved a mean accuracy (ACC) of 0.85, an area under the curve (AUC) of 0.92, and a receiver operating characteristic (ROC) score of 0.92. Conclusion In summary, this method demonstrated excellent performance in predicting Parkinson’s disease, allowing for more accurate predictions of Parkinson’s disease.
Enhancing chickpea yield through the application of sulfur and sulfur-oxidizing bacteria
Quantifying the genetic origins of body plan scaling
Effects of pre-oxidation temperature and air volume on oxidation thermogravimetric and functional group change of lignite
To investigate the impact of the oxidation temperature and variations in airflow conditions on coal spontaneous combustion characteristics, pre-oxidized coal samples were prepared using a programmed temperature rise method. Synchronous thermal analysis experiments and Fourier transform infrared spectroscopy were conducted to explore changes in the thermal effects and functional group content of the coal samples, respectively. The results indicate that variations in pre-oxidation conditions primarily in fluence the activation temperature and maximum weight loss temperature of the coal samples, while exerting a lesser impact on the critical temperature and ignition point. Variations in air volume conditions predominantly affect the content of Ar-C-O- and -CH2 & -CH3 in the oxygen-containing functional group region. The trend of the average activation energy within a conversion rate range of 0.2 to 0.6 of pre-oxidized coal samples changing with the increased of pre-oxidation temperature under the air flow conditions of 25mL/min and 50mL/min is consistent, but opposite to that under the air flow conditions of 100mL/min and 200mL/min. Compared to raw coal, under an airflow rate of 50 mL/min and when oxidized to 110°C, the coal sample exhibits an increase in the content of OH…OH, accompanied by reductions in the critical temperature, activation temperature, ignition point, and maximum weight loss temperature to varying degrees, thereby rendering it more susceptible to oxidative spontaneous combustion.
Prediction of late-onset depression in the elderly Korean population using machine learning algorithms
The origin of color categories
To what extent does concept formation require language? Here, we exploit color to address this question and ask whether macaque monkeys have color concepts evident as categories. Macaques have similar cone photoreceptors and central visual circuits to humans, yet they lack language. Whether Old World monkeys such as macaques have consensus color categories is unresolved, but if they do, then language cannot be required. If macaques do not have color categories, then color categories in humans are unlikely to derive from innate properties of visual encoding and likely to depend on cognitive abilities such as language that differ between monkeys and humans. We tested macaques by adapting a match-to-sample paradigm used in humans to uncover color categories from errors in matches, and we analyzed the data using computational simulations that assess the possibility of unrecognized distortions in the perceptual uniformity of color space. The results provide evidence that humans have consensus cognitive color categories and macaques do not. One animal showed evidence for a private color category, demonstrating that monkeys have the capacity to form color categories even if they do not form consensus color categories. Taken together, the results imply that consensus color categories in humans, for which there is ample evidence, must depend upon language or other cognitive abilities.
The role of mitochondrial dysfunction in the cytotoxic synergistic effect of gemcitabine and arsenic on breast cancer
Breast cancer is the most common type of cancer in women worldwide. A common approach to cancer treatment in clinical practice is to use a combination of drugs to enhance the anticancer activity of drugs while reducing their side effects. In this regard, we evaluated the effectiveness of combined treatment with gemcitabine (GCB) and arsenic (ATO) and how they affect the cell death pathway in cancer cells. Cytotoxic activity of drugs individually or combined against MDA-MB-231 and MCF-7 was performed by MTT method and isobolographic analysis was used to determine the interaction between these factors. The combination of ATO and GCB showed synergistic anti-cancer activity (CI < 1) in both cancer cell lines. The combination of ATO and GCB induced sub-G1 phase arrest, apoptosis and death rates in MCF-7 and MDA-MB-231 cells. The apoptotic response induced by the combination of GCB and ATO was dependent on caspase 3/7. Combined treatment with mitochondrial membrane potential (MMP) reduction and increased reactive oxygen species (ROS) production caused mitochondrial dysfunction. Co-treatment significantly reduced catalase (CAT) activity in both cancer cells compared to the control group and cells treated with each monotherapy. A significant decrease in cellular GSH was observed in cancer cells treated with ATO and GCB. In addition, migration and invasion were significantly reduced in breast cancer cells treated with the combination of ATO and GCB compared to cells treated with ATO and GCB. In conclusion, the combined treatment of ATO and GCB synergistically increased the anti-cancer activity, and these findings provide an effective approach for the treatment of breast cancer. To the best of our knowledge, this is the first study showing promising results for combination therapy with ATO and GCB in breast cancer.
Heavy metals concentrations in commercial organic fertilizers and the potential risk of fertilization into soils
Pseudogap in electron-doped cuprates: Strong correlation leading to band splitting
The pseudogap phenomena have been a long-standing mystery of the cuprate high-temperature superconductors. The pseudogap in the electron-doped cuprates has been attributed to band folding due to antiferromagnetic (AFM) long-range order or short-range correlation. We performed an angle-resolved photoemission spectroscopy study of the electron-doped cuprates Pr 1.3− x La 0.7 Ce x CuO 4 showing spin-glass, disordered AFM behaviors, and superconductivity at low temperatures and, by measurements with fine momentum cuts, found that the gap opens on the unfolded Fermi surface rather than the AFM Brillouin zone boundary. The gap did not show a node, following the full symmetry of the Brillouin zone, and its magnitude decreased from the zone-diagonal to ( π ,0) directions, opposite to the hole-doped case. These observations were reproduced by cluster dynamical-mean-field-theory calculation, which took into account electron correlation precisely within a (CuO 2 ) 4 cluster. The present experimental and theoretical results are consistent with the mechanism that electron or hole doping into a Mott insulator creates an in-gap band that is separated from the upper or lower Hubbard band by the pseudogap.
Factors associated with the delay in diagnosis of extrapulmonary tuberculosis at the patient and health system level: A study from a rural setting in India
Background With the proportion of tuberculosis cases that are extrapulmonary tuberculosis (EPTB) increasing in recent years, understanding and addressing factors contributing to the prolonged time to diagnosis (TTD) of EPTB patients is vital. Methods We enrolled presumptive EPTB patients for a cohort study from 2018–2020 in Ujjain, India. Based on a structured questionnaire, the patients were interviewed for socio-demographic and clinical information, including previously visited health facilities (HF) for this illness. We analysed patients’ TTD, healthcare access, and referral pathways. Findings EPTB (54%) and non-TB (58%) patients visited dispensaries during their first visit to a formal HF. Patients visited multiple HFs, including dispensaries (54%) and regional hospitals (32%), during 1–4 visits but did not receive an appropriate diagnosis. Less than 2% of the patients accessed private HFs. Most of the adult EPTB (83%) and non-TB (76%) patients were self-referred to our study site, where they were diagnosed. Our statistical models highlighted low-middle income groups, longer distances and longer travel time to HFs, and potentially less-empowered occupations as housewives with a prolonged TTD. Patients with a longer wait, including travel time, had a shorter TTD. Conclusion We found individual, societal-level, and structural barriers to healthcare access and utilisation and their association with diagnostic delay among adult and paediatric EPTB patients.
Meta-analysis of the effect of non-pharmacological interventions on the development of dysgeusia in patients undergoing radiotherapy for head and neck squamous cell carcinoma
Protein dynamics underlies strong temperature dependence of heat receptors
Ion channels are generally allosteric proteins, involving specialized stimulus sensor domains conformationally linked to the gate to drive channel opening. Temperature receptors are a group of ion channels from the transient receptor potential family. They exhibit an unprecedentedly strong temperature dependence and are responsible for temperature sensing in mammals. Despite intensive studies, however, the nature of the temperature sensor domain in these channels remains elusive. By direct calorimetry of TRPV1 proteins, we have recently provided a proof of principle that temperature sensing by ion channels may diverge from the conventional allosterity theory; rather it is intimately linked to inherent thermal instability of channel proteins. Here, we tackle the generality of the hypothesis and provide key molecular pieces of evidence on the coupling of thermal transitions in the channels. We show that while wild-type channels possess a single concerted thermal transition peak, the chimera, in which strong temperature dependence becomes disrupted, results in multitransition peaks, and the activation enthalpies are accordingly reduced. The data show that the coupling with protein unfolding drives up the energy barrier of activation, leading to a strong temperature dependence of opening. Furthermore, we pinpoint the proximal N-terminus of the channels as a linchpin in coalescing different parts of the channels into concerted activation. Thus, we suggest that coupled interaction networks in proteins underlie the strong temperature dependence of temperature receptors.
Solar radiation model and optimization of asymmetric large-span externally insulated plastic greenhouses
To improve the light environment of asymmetric large-span externally insulated plastic greenhouses, a solar radiation model that considers the projection path equations of the insulation quilts and validated the model was established. The model was employed to investigate the impact of different heights, spans, and north lighting projection lengths on the greenhouses’ light environment. The results revealed that ground radiation interception, a key component of winter lighting, was most influenced by height, followed by span, and least influenced by the projection length of the north lighting roof. Additionally, ground radiation spatial uniformity was most affected by height, followed by the projection length of the north lighting roof, and least influenced by span. The optimization objectives for solar radiation were set to maximize solar radiation interception and minimize the coefficient of variation. The optimal structural parameters for the asymmetric large-span externally insulated plastic greenhouse were determined using the NSGA-II method and the entropy weight-TOPSIS method: the height of 6.97 m, and the projection length of north lighting roof is 7.44 m for a greenhouse with a span of 20.00 m. Compared to the initial greenhouse, the optimized design enhances both radiation interception performance and ensures uniform light distribution. These results offer valuable theoretical guidance for greenhouse construction.
Application of hybrid gate recurrent unit for in-store trajectory prediction based on indoor location system
Tungsten is utilized for lactate consumption and SCFA production by a dominant human gut microbe <i>Eubacterium limosum</i>
Eubacterium limosum is a dominant member of the human gut microbiome and produces short-chain fatty acids (SCFAs). These promote immune system function and inhibit inflammation, making this microbe important for human health. Lactate is a primary source of gut SCFAs but its utilization by E. limosum has not been explored. We show that E. limosum growing on lactate takes up added tungstate rather than molybdate and produces the SCFAs acetate and butyrate, but not propionate. The genes encoding an electron bifurcating, tungsten-containing oxidoreductase (WOR1) and a tungsten-containing formate dehydrogenase (FDH), along with an electron bifurcating lactate dehydrogenase (LCT), lactate permease, and enzymes of the propanediol pathway, are all up-regulated on lactate compared to growth on glucose. Lactate metabolism is controlled by a GntR-family repressor (LctR) and two global regulators, Rex and CcpA, where Rex in part controls W storage and tungstopyranopterin (Tuco) biosynthesis. Tuco-dependent riboswitches, along with CcpA, also control two iron transporters, consistent with the increased iron demand for many iron-containing enzymes, including WOR1 and FDH, involved in SCFA production. From intracellular aldehyde concentrations and the substrate specificity of WOR1, we propose that WOR1 is involved in detoxifying acetaldehyde produced during lactate degradation. Lactate to SCFA conversion by E. limosum is clearly highly tungstocentric and tungsten might be an overlooked micronutrient in the human microbiome and in overall human health.
The ambiguous role of partially protected marine protected areas in Australia: Results from a systematic literature review
Marine protected areas (MPAs) are an important tool in helping to protect biodiversity in the oceans. Recent ratification of the Kunming-Montreal Global Biodiversity Framework (GBF) has ensured that globally we are committed to effectively protecting 30% of the world’s oceans by 2030, in MPAs. In Australia there is considerable interest in the potential benefits that partially protected areas (PPAs) may provide. However, a consistent definition of a PPA is currently lacking, and urgently needed to conduct quantitative analyses of PPAs. We conducted a systematic literature review to understand the current knowledge surrounding PPAs and their potential benefits. We define a PPA, characterise PPA implementation in Australia, and present results for the outcomes of PPAs in terms of ecological, economic, and social indicators. Our review suggests that although 45% of Australia’s marine environment is within MPAs, 61% of MPAs provide only partial protection. The Northern Territory (100%), New South Wales (81%), and Queensland (79.8%) have the highest percentage of MPAs that are partially protected, compared to Tasmania which has the smallest percentage of partially protected MPAs (13.12%). Tasmania also has the smallest percentage cover of MPAs (6.49% state waters). Most PPA management plans did not contain quantifiable Key Performance Indicators (KPIs) to be able to effectively monitor the progress of these PPAs against the stated outcomes. We find the benefits of PPAs to be ambiguous: PPAs generally provide benefits when compared to ‘open’ ocean, however this is not a consistent result. There are no PPAs that provide greater overall benefits when compared to fully protected MPAs. Only one state (South Australia) and the Commonwealth (Australian Marine Parks) are collecting publicly available baseline data to facilitate quantitative monitoring of PPAs. Contrary to fisheries management, there were no plans of action if the declared MPAs and PPAs failed to meet their declared objectives and goals. Some PPAs within Australia appear to be incompatible with conservation priorities according to the recent “MPA Guide” classification framework. This study highlights the need for clearer management rationale and plans for PPAs in Australia, as these comprise the majority of MPAs in Australia’s Exclusive Economic Zone.