Hasil untuk "Biology (General)"

Stella Brown, Nicolas Preisig, Autumn Davis et al.

Understanding how protein mutations affect protein structure is essential for advancements in computational biology and bioinformatics. We introduce PRIMRose, a novel approach that predicts energy values for each residue given a mutated protein sequence. Unlike previous models that assess global energy shifts, our method analyzes the localized energetic impact of double amino acid insertions or deletions (InDels) at the individual residue level, enabling residue-specific insights into structural and functional disruption. We implement a Convolutional Neural Network architecture to predict the energy changes of each residue in a protein mutation. We train our model on datasets constructed from nine proteins, grouped into three categories: one set with exhaustive double InDel mutations, another with approximately 145k randomly sampled double InDel mutations, and a third with approximately 80k randomly sampled double InDel mutations. Our model achieves high predictive accuracy across a range of energy metrics as calculated by the Rosetta molecular modeling suite and reveals localized patterns that influence model performance, such as solvent accessibility and secondary structure context. This per-residue analysis offers new insights into the mutational tolerance of specific regions within proteins and provides higher interpretable and biologically meaningful predictions of InDels' effects.

Swarnavo Basu, Karen Alim

Flows are essential to transport resources over large distances. As soon as diffusion becomes time-limiting, flows are needed. Flows are key for the function of multiple human organs, from the blood vasculature to the lungs, the digestive tract, the lymphatic system, and many more. While physics governs the flow dynamics, biology's response to flows governs the flow network architecture. We start with the fluid physics of Stokes flow, the prerequisite to describe the flows in biological flow networks. Then we explore how the network adaptation dynamics of biological flow networks reorganize network architecture to minimize flow dissipation or homogenize transport, storing memories of past flows along the way.

Arlie R. Macdonald, Maddie E. James, Jonathan D. Mitchell et al.

Mapping genotypes to phenotypes (G2P) is a fundamental goal in biology. So called PhyloG2P methods are a relatively new set of tools that leverage replicated evolution in phylogenetically independent lineages to identify genomic regions associated with traits of interest. Here, we review recent developments in PhyloG2P methods, focusing on three key areas: methods based on replicated amino acid substitutions, methods detecting changes in evolutionary rates, and methods analysing gene duplication and loss. We discuss how the definition and measurement of traits impacts the utility of these methods, arguing that focusing on simple rather than compound traits will lead to more meaningful genotype-phenotype associations. We advocate for the use of methods that work with continuous traits directly rather than collapsing them to binary representations. We examine the strengths and limitations of different approaches to modeling genetic replication, highlighting the importance of explicit modeling of evolutionary processes. Finally, we outline promising future directions, including the integration of population-level variation, as well as epigenetic and environmental information. No one method is likely to identify all genomic regions of interest, so we encourage users to apply multiple methods that are capable of detecting a wide range of associations. The overall aim of this review is to provide practitioners a roadmap for understanding and applying PhyloG2P methods.

Paulo Borges, Sónia Bettencourt, Dejalme Vargas et al.

From 2011 to 2024, the Azorean Government tested two coordinated monitoring programmes across the archipelago to survey four invasive termite species: the West Indian drywood termite, Cryptotermes brevis (Walker, 1853); the yellow-necked drywood termite, Kalotermes flavicollis (Fabricius, 1793); the Western European subterranean termite, Reticulitermes grassei Clément, 1978; and the eastern subterranean termite, Reticulitermes flavipes (Kollar, 1837). The monitoring programme was mostly directed to the detection of C. brevis in new locations. Drywood species were detected on multiple islands, with C. brevis established on six islands (from west to east: Faial, Pico, São Jorge, Terceira, São Miguel and Santa Maria) and exhibiting the highest infestation densities in the urban centres of the three most important islands in terms of economic activity and human population (São Miguel, Terceira and Faial). Kalotermes flavicollis occurs more sporadically, primarily along the south coasts of Terceira, São Miguel and southeast coast of Faial and seldom attains the pest status of C. brevis. In contrast, the two Reticulitermes species remain restricted to localised subterranean infestations: Reticulitermes grassei in Horta (Faial) and R. flavipes near Lajes Air Force Base (Terceira), each detected via house inspection visits. Collectively, these efforts provide the first comprehensive, archipelago-wide dataset on termite presence, laying the groundwork for targeted Integrated Pest Management strategies in the Azores.Records of Cryptotermes brevis overwhelmingly dominated the monitoring data, comprising 1,801 of the 1,832 total events (98%), a pattern consistent with previous surveys of its rapid spread in the Azorean urban environment. These detections were heavily concentrated on two islands: Terceira (n = 919) and São Miguel (n = 755). In contrast, Faial, Pico and Santa Maria each yielded roughly 40 records and São Jorge only seven. Annual trap‐capture counts across all islands increased steadily from approximately 40 captures in 2011 to 154 in 2024, peaking at 185 in 2023.Kalotermes flavicollis was the second most frequently recorded species (n = 24), with most records originating on São Miguel, mirroring its more restricted distribution. The two subterranean termites, Reticulitermes grassei and R. flavipes, were documented exclusively on Faial and Terceira, respectively, consistent with their historically limited foothold in the archipelago.Now established on every surveyed island and exhibiting an upward trajectory in annual detection counts, C. brevis remains the foremost urban termite threat in the Azores. To forestall further structural outbreaks, Integrated Pest Management should place sustained emphasis on early detection — through year-round trap checks — and on heightened public awareness, by encouraging residents to report both the characteristic pin-sized faecal pellets and any termite occurrence observed during swarming periods.

Aida Meto

Bearing in mind the expression, “<i>The art challenges the technology, and the technology inspires the art</i>”, we say that oral surgery is changing rapidly due to the introduction of new technologies that improve the way surgical treatments are planned and performed [...]

Xiao-Song Chen, Feng Chen, Shu-Jia He et al.

Aim To investigate the comprehensive expression levels and possible molecular mechanisms of Anaphase Promoting Complex Subunit 1 (ANAPC1) in lung squamous cell carcinoma (LUSC).Methods Data from 2,031 samples were combined to evaluate ANAPC1 mRNA levels, and 118 samples were collected for immunohistochemical (IHC) analysis. High-expression co-expressed genes (HECEGs) associated with ANAPC1 were analyzed for signaling pathways. Clinical significance, immune computations, and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) validation of ANAPC1’s role in LUSC were assessed. Molecular docking evaluated binding affinity with potential therapeutics.Results ANAPC1 mRNA was significantly upregulated in LUSC (SMD = 1.97, 95% CI [1.26–2.67]). Protein-level analysis confirmed this upregulation (p < 0.001). Most HECEGs associated with ANAPC1 were enriched in cell cycle pathways. Higher ANAPC1 expression correlated with poorer survival in LUSC patients (HR = 1.11, 95% CI: 1–1.49). ANAPC1 expression was higher in males and N1-stage vs. females and N0-stage; lower in grade I vs. II/III. Overexpression reduces immune cell infiltration and immunotherapy effectiveness, while knockdown inhibits cell proliferation. Drug sensitivity and docking analyses identified tenovin-1, carboxyatractyloside, and phycocyanobilin as potential antitumor agents targeting ANAPC1.Conclusion The elevated expression of ANAPC1 might play a role in LUSC advancement and progression through its participation in cell growth-related pathways.

Justyna Adamczyk

Coal sludge, a fine-grained by-product of hard coal benefit, comprises a mixture of coal particles and mineral and organic matter. Generated during sedimentation and dewatering processes in preparation plants, it is typically recovered as a semi-solid filter cake. The material has potential applications in energy production and, with appropriate processing and stabilization, could be utilized in geotechnical facilities. The strength properties defined by the internal friction angle and cohesion, as well as the deformation properties expressed by compressibility, are among the most important mechanical characteristics of soil. This article presents tests of coal sludge, for which the internal friction angle, cohesion, and oedometric primary and secondary moduli were determined. The material was prepared at its optimum moisture content and maximum dry density prior to testing. In the direct shear test, using a shear box of 6 × 6 cm, each sample was consolidated for 24 h under the applied vertical stress, under which it was subsequently sheared. The shear rate was constant at 0.01 mm/min, and the test was conducted up to 10% horizontal deformation. The vertical stresses applied ranged from 50 to 200 kPa. In the oedometer test, samples were prepared to fit the dimensions of the oedometer ring, and each subsequent load stage was applied after 24 h. The range of vertical stresses in this test was from 12.5 to 400 kPa. The results of the direct shear test (φ = 24°, c = 28 kPa) are similar to the strength parameters typically obtained for medium-cohesive soils, such as sandy silt (φ = 22°, c = 25 kPa. The results of the compressibility tests (0.89 MPa < M₀ < 6.35 MPa) correspond to values characteristic of organic soils, for example, organic silts (0.5 MPa < M₀ < 5 MPa). Moreover, analysis of the consolidation curves showed that up to a vertical stress of 100 kPa, coal sludge does not exhibit rheological behavior. The obtained results indicate that coal sludge, when compacted up to its optimum moisture content and to an adequate dry density, can be effectively utilized for geotechnical applications, such as the construction of isolation barriers, as a component of geotechnical mixtures, or as a sealing material for the reclamation of post-mining areas.

Robert K. Colwell

Dylan Galt, Langte Ma

We study generalized anti-self-dual instantons defined over Riemannian manifolds equipped with a parallel codimension-$4$ differential form. In particular, for product Riemannian manifolds possessing such a form, we study dimension reduction phenomena, finding a topological criterion for bundles which, when satisfied, allows for a complete characterization of dimension reduction for the corresponding moduli space of generalized ASD instantons. By establishing an integrability result for families of connections, we then deduce explicit descriptions for these moduli spaces, including those of Hermitian Yang--Mills connections, $G_2$-, and $\Spin(7)$-instantons. When one factor in the product is a $4$-manifold, we establish well-behaved compactifications for these moduli spaces.

Donald P. Cameron, Jirawas Sornkom, Sameerh Alsahafi et al.

While genotoxic chemotherapeutic agents are among the most effective tools to combat cancer, they are often associated with severe adverse effects caused by indiscriminate DNA damage in non-tumor tissue as well as increased risk of secondary carcinogenesis. This study builds on our previous work demonstrating that the RNA Polymerase I (Pol I) transcription inhibitor CX-5461 elicits a non-canonical DNA damage response and our discovery of a critical role for Topoisomerase 2α (Top2α) in the initiation of Pol I-dependent transcription. Here, we identify Top2α as a mediator of CX-5461 response in the murine Eµ-<i>Myc</i> B lymphoma model whereby sensitivity to CX-5461 is dependent on cellular Top2α expression/activity. Most strikingly, and in contrast to canonical Top2α poisons, we found that the Top2α-dependent DNA damage induced by CX-5461 is preferentially localized at the ribosomal DNA (rDNA) promoter region, thereby highlighting CX-5461 as a loci-specific DNA damaging agent. This mechanism underpins the efficacy of CX-5461 against certain types of cancer and can be used to develop effective non-genotoxic anticancer drugs.

Joji Tani, Tsutomu Masaki, Kyoko Oura et al.

Chronic hepatitis C virus (HCV) infection is associated with an increased risk of extrahepatic cancers, particularly non-Hodgkin lymphoma. The introduction of direct-acting antivirals (DAAs) has revolutionized HCV therapy, resulting in high cure rates. However, concerns have been raised about potential effects on cancer risk. This review summarizes the current evidence on extrahepatic cancer risk in HCV-infected patients treated with DAAs. We examined epidemiologic data on HCV-associated extrahepatic cancers and explored potential mechanisms linking HCV to carcinogenesis outside the liver. Studies evaluating cancer outcomes after DAA therapy were critically reviewed while considering methodological challenges. While some studies suggested a reduced risk of extrahepatic cancers after DAA therapy, others showed no significant change. Limitations included short follow-up periods and confounding variables. Immunological changes following rapid HCV clearance may have complex effects on cancer risk. Long-term prospective studies and mechanistic investigations are needed to fully elucidate the relationship between DAA therapy and extrahepatic cancer risk in HCV patients. Clinicians should remain vigilant for extrahepatic malignancies in this population.

Asier Léniz, Alfredo Fernández-Quintela, Sara Arranz et al.

Background: Adipokines, as well as the fatty acid profile of red blood cell (RBC) membranes, are known to play important roles in the development and progression of metabolic complications induced by obesity. Thus, the objective of this study is to compare the serum adipokine profile and the RBC membrane fatty acid profile of normal-weight and obese adults, and to analyze their relationship with serum biochemical parameters. Methods: An observational case–control study was performed in 75 normal-weight and obese adult subjects. Biochemical serum parameters, eight serum adipokines and the RBC membrane fatty acid profiles were measured. Associations between parameters were established using regression analysis. Results: Subjects with obesity showed increased levels of leptin, fibroblast growth factor 21 (FGF21) and overexpressed nephroblastoma (NOV/CCN3), decreased adiponectin, and similar levels of vaspin and chemerin compared to normal-weight subjects. Significant positive and negative correlations were found with triglycerides and high-density lipoprotein-cholesterol (HDL-c), respectively. An increase in the total ω-6 fatty acids in the RBC membrane fatty acid profiles in subjects with obesity was observed, because of higher levels of both dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), and decreased total ω-3 fatty acids, mainly due to lower levels of docosahexaenoic acid (DHA). The ω-6/ω-3 ratio in the RBCs was significantly higher, suggesting an inflammatory status, as was also suggested by a reduced adiponectin level. A negative association between DGLA and adiponectin, and a positive association between DHA and serum triglycerides, was observed. Conclusions: Important alterations in serum adipokine and RBC fatty acid profiles are found in subjects with obesity.

Xiaoyu Gu, Zixuan Guo, Maolin Cai et al.

Objective: Diaphragm pacing (DP) is a long-term and effective respiratory assist therapy for patients with central alveolar hypoventilation and high cervical spinal cord injury. The existing DP system has some limitations, especially high price, inconvenience preoperative evaluation methods and diaphragm fatigue easily. Our objective was to develop a DP system and evaluated reliability through hardware testing and animal experiments.Methods: A DP system with bidirectional constant current was designed, manufactured and tested. Effects of a wide range of stimulus amplitudes (range: .5–2.5 mA) and frequencies (range: 10–250 Hz) on airflow and corresponding inspired volume were investigated during DP. Differences in airflow characteristics under various stimulation parameters were evaluated using power function. ECG interference in diaphragm electromyography (EMGdi) was filtered out using stationary wavelet transform to obtain pure EMGdi (EMGdip). 80-min period with a tendency for diaphragm fatigue by root mean square (RMS) and centroid frequency (fc) of EMGdip was studied.Results: The increase of stimulus frequency and amplitude in animals resulted in different degrees of increase in envoked volume. Significant difference in Airflow Index (b) between anesthesia and DP provided a simple, non-invasive and feasible solution for phrenic nerve conduction function test. Increased stimulation duration with the developed DP system caused less diaphragm fatigue.Conclusion: A modular, inexpensive and reliable DP was successfully developed. Its effectiveness was confirmed in animal experiments.Significance: This study is useful for design of future implantable diaphragmatic pacemakers for improving diaphragm fatigue and convenient assessment of respiratory activity in experiments.

Fotios S. Konstantakopoulos, Eleni I. Georga, Dimitrios I. Fotiadis

<italic>Goal</italic>: The modern way of living has significantly influenced the daily diet. The ever-increasing number of people with obesity, diabetes and cardiovascular diseases stresses the need to find tools that could help in the daily intake of the necessary nutrients. <italic>Methods:</italic> In this paper, we present an automated image-based dietary assessment system of Mediterranean food, based on: 1) an image dataset of Mediterranean foods, 2) on a pre-trained Convolutional Neural Network (CNN) for food image classification, and 3) on stereo vision techniques for the volume and nutrition estimation of the food. We use a pre-trained CNN in the Food-101 dataset to train a deep learning classification model employing our dataset Mediterranean Greek Food (MedGRFood). Based on the EfficientNet family of CNNs, we use the EfficientNetB2 both for the pre-trained model and its weights evaluation, as well as for classifying food images in the MedGRFood dataset. Next, we estimate the volume of the food, through 3D food reconstruction of two images taken by a smartphone camera. The proposed volume estimation subsystem uses stereo vision techniques and algorithms, and needs the input of two food images to reconstruct the point cloud of the food and to compute its quantity. <italic>Results:</italic> The classification accuracy where true class matches with the most probable class predicted by the model (Top-1 accuracy) is 83.8&#x0025;, while the accuracy where true class matches with any one of the 5 most probable classes predicted by the model (Top-5 accuracy) is 97.6&#x0025;, for the food classification subsystem. The food volume estimation subsystem achieves an overall mean absolute percentage error 10.5&#x0025; for 148 different food dishes. <italic>Conclusions:</italic> The proposed automated image-based dietary assessment system provides the capability of continuous recording of health data in real time.

Tyler Cody, Niloofar Shadab, Alejandro Salado et al.

Engineering methods are centered around traditional notions of decomposition and recomposition that rely on partitioning the inputs and outputs of components to allow for component-level properties to hold after their composition. In artificial intelligence (AI), however, systems are often expected to influence their environments, and, by way of their environments, to influence themselves. Thus, it is unclear if an AI system's inputs will be independent of its outputs, and, therefore, if AI systems can be treated as traditional components. This paper posits that engineering general intelligence requires new general systems precepts, termed the core and periphery, and explores their theoretical uses. The new precepts are elaborated using abstract systems theory and the Law of Requisite Variety. By using the presented material, engineers can better understand the general character of regulating the outcomes of AI to achieve stakeholder needs and how the general systems nature of embodiment challenges traditional engineering practice.

Ahmad Mohsenimanesh, Evgueniy Entchev, Filip Bosnjak

Forecasting the aggregate charging load of a fleet of electric vehicles (EVs) plays an important role in the energy management of the future power system. Therefore, accurate charging load forecasting is necessary for reliable and efficient power system operation. A hybrid method that is a combination of the similar day (SD) selection, complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN), and deep neural networks is proposed and explored in this paper. For the SD selection, an extreme gradient boosting (XGB)-based weighted k-means method is chosen and applied to evaluate the similarity between the prediction and historical days. The CEEMDAN algorithm, which is an advanced method of empirical mode decomposition (EMD), is used to decompose original data, to acquire intrinsic mode functions (IMFs) and residuals, and to improve the noise reduction effect. Three popular deep neural networks that have been utilized for load predictions are gated recurrent units (GRUs), long short-term memory (LSTM), and bidirectional long short-term memory (BiLSTM). The developed models were assessed on a real-life charging load dataset that was collected from 1000 EVs in nine provinces in Canada from 2017 to 2019. The obtained numerical results of six predictive combination models show that the proposed hybrid SD-CEEMDAN-BiLSTM model outperformed the single and other hybrid models with the smallest forecasting mean absolute percentage error (MAPE) of 2.63% Canada-wide.

Loganathan Ponnusamy, Reuben Garshong, Bryan S. McLean et al.

Chiggers are vectors of rickettsial pathogenic bacteria, <i>Orientia</i> spp., that cause the human disease, scrub typhus, in the Asian–Pacific area and northern Australia (known as the Tsutsugamushi Triangle). More recently, reports of scrub typhus in Africa, southern Chile, and the Middle East have reshaped our understanding of the epidemiology of this disease, indicating it has a broad geographical distribution. Despite the growing number of studies and discoveries of chigger-borne human disease outside of the Tsutsugamushi Triangle, rickettsial pathogens in chigger mites in the US are still undetermined. The aim of our study was to investigate possible <i>Rickettsia</i> DNA in chiggers collected from rodents in North Carolina, USA. Of 46 chiggers tested, 47.8% tested positive for amplicons of the 23S-5S gene, 36.9% tested positive for 17 kDa, and 15.2% tested positive for <i>gltA</i>. Nucleotide sequence analyses of the <i>Rickettsia</i>-specific 23S-5S intergenic spacer (IGS), 17 kDa, and <i>gltA</i> gene fragments indicated that the amplicons from these chiggers were closely related to those in <i>R. felis</i>, <i>R. conorii</i>, <i>R. typhi</i>, and unidentified <i>Rickettsia</i> species. In this study, we provide the first evidence of <i>Rickettsia</i> infection in chiggers collected from rodents within the continental USA. In North Carolina, a US state with the highest annual cases of spotted fever rickettsioses, these results suggest chigger bites could pose a risk to public health, warranting further study.

Yu Wang, Kun Zhou

Two-dimensional (2D) materials have exhibited great potential for replacing costly Pt for oxygen reduction reaction (ORR) because of their distinctive structural features and high pre-site activity. However, their performance is generally hindered by the limited density of active sites (e.g., at the layer edges). Although they feature a high exposure of surface sites, these sites are typically inert for ORR. Herein, through density functional theory calculations, we propose a promising ORR catalyst candidate, a 2D TaTe2 nanosheet, which has an intrinsic high basal-plane activity. Both of the thermodynamic and kinetic processes are explored, which demonstrates that the basal-plane Te sites of the TaTe2 nanosheet have great potential for facilitating ORR. Specifically, we construct a microkinetic model of ORR proceeding on TaTe2, which unveils its dynamic intermediate coverage under different electrode potentials and identifies the dominating associative pathway. The theoretical half-wave potential of TaTe2 is predicted to be 0.87 V, which exceeds those of the well-established Pt (111) and Fe–N–C single-atom catalysts computed at the same level. This study not only presents the first 2D, non-Pt ORR catalyst candidate with an intrinsic basal-plane activity but also offers a rational methodology for unveiling the mechanism/activity of ORR and other electrochemical reactions.

Haesoo Jung, Da-Min Jung, Sang-Soo Lee et al.

The crosstalk between androgens and Wnt signaling pathways is critical in the hair growth cycle. Therefore, natural products that target these two pathways for the inhibition of hair loss are sought after. In this study, we investigated the effect of water extracts of Mangifera indica leaves (WEML) on hair growth. WEML treatment significantly reduced the expression levels of both dickkopf-1 (DKK1) and type 2 5α-reductase (SRD5A2) involved in Wnt signal suppression activity and dihydrotestosterone (DHT) synthesis, respectively, in human follicle dermal papilla cells (HFDP). In addition, WEML treatment effectively upregulated Wnt target genes and downregulated DKK1 expression that was increased by DHT treatment. Degranulation analysis in rat basophilic leukemia mast cell line (RBL-2H3) using β-hexosaminidase release assay confirmed that WEML did not exhibit allergenic activity. Furthermore, hair growth was significantly enhanced in in vivo mice model treated with WEML. These results suggest that M. indica leave extract contains bioactive materials that can be used to treat hair loss.

Inga A. Frøland Steindal, D. Whitmore

Zebrafish represent the one alternative vertebrate, genetic model system to mice that can be easily manipulated in a laboratory setting. With the teleost Medaka (Oryzias latipes), which now has a significant following, and over 30,000 other fish species worldwide, there is great potential to study the biology of environmental adaptation using teleosts. Zebrafish are primarily used for research on developmental biology, for obvious reasons. However, fish in general have also contributed to our understanding of circadian clock biology in the broadest sense. In this review, we will discuss selected areas where this contribution seems most unique. This will include a discussion of the issue of central versus peripheral clocks, in which zebrafish played an early role; the global nature of light sensitivity; and the critical role played by light in regulating cell biology. In addition, we also discuss the importance of the clock in controlling the timing of fundamental aspects of cell biology, such as the temporal control of the cell cycle. Many of these findings are applicable to the majority of vertebrate species. However, some reflect the unique manner in which “fish” can solve biological problems, in an evolutionary context. Genome duplication events simply mean that many fish species have more gene copies to “throw at a problem”, and evolution seems to have taken advantage of this “gene abundance”. How this relates to their poor cousins, the mammals, remains to be seen.