Scientific Reports

Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.

To be effective as a drug, a potent molecule must reach its target in the body in sufficient concentration, and stay there in a bioactive form long enough for the expected biologic events to occur. Drug development involves assessment of absorption, distribution, metabolism and excretion (ADME) increasingly earlier in the discovery process, at a stage when considered compounds are numerous but access to the physical samples is limited. In that context, computer models constitute valid alternatives to experiments. Here, we present the new SwissADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar. Easy efficient input and interpretation are ensured thanks to a user-friendly interface through the login-free website http://www.swissadme.ch. Specialists, but also nonexpert in cheminformatics or computational chemistry can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavours.

Polycyclic aromatic compounds (PACs) are known due to their mutagenic activity. Among them, 2-nitrobenzanthrone (2-NBA) and 3-nitrobenzanthrone (3-NBA) are considered as two of the most potent mutagens found in atmospheric particles. In the present study 2-NBA, 3-NBA and selected PAHs and Nitro-PAHs were determined in fine particle samples (PM 2.5) collected in a bus station and an outdoor site. The fuel used by buses was a diesel-biodiesel (96:4) blend and light-duty vehicles run with any ethanol-to-gasoline proportion. The concentrations of 2-NBA and 3-NBA were, on average, under 14.8 µg g⁻¹ and 4.39 µg g⁻¹, respectively. In order to access the main sources and formation routes of these compounds, we performed ternary correlations and multivariate statistical analyses. The main sources for the studied compounds in the bus station were diesel/biodiesel exhaust followed by floor resuspension. In the coastal site, vehicular emission, photochemical formation and wood combustion were the main sources for 2-NBA and 3-NBA as well as the other PACs. Incremental lifetime cancer risk (ILCR) were calculated for both places, which presented low values, showing low cancer risk incidence although the ILCR values for the bus station were around 2.5 times higher than the ILCR from the coastal site.

QuPath is new bioimage analysis software designed to meet the growing need for a user-friendly, extensible, open-source solution for digital pathology and whole slide image analysis. In addition to offering a comprehensive panel of tumor identification and high-throughput biomarker evaluation tools, QuPath provides researchers with powerful batch-processing and scripting functionality, and an extensible platform with which to develop and share new algorithms to analyze complex tissue images. Furthermore, QuPath’s flexible design makes it suitable for a wide range of additional image analysis applications across biomedical research.

Nghiên cứu trước đây của chúng tôi đã chứng minh sự gia tăng biểu hiện của protein sốc nhiệt (Hsp) 90 trong da của bệnh nhân xơ cứng bì hệ thống (SSc). Mục tiêu của chúng tôi là đánh giá nồng độ Hsp90 trong huyết tương ở bệnh nhân SSc và xác định mối liên quan của nó với các đặc điểm liên quan đến SSc. Có 92 bệnh nhân SSc và 92 người đối chứng khỏe mạnh được sắp xếp theo độ tuổi và giới tính được tuyển chọn cho phân tích cắt ngang. Phân tích dọc bao gồm 30 bệnh nhân bị SSc kèm bệnh phổi kẽ (ILD) được điều trị thường xuyên với cyclophosphamide. Hsp90 gia tăng ở bệnh nhân SSc so với nhóm đối chứng khỏe mạnh. Hsp90 tương quan dương tính với protein C phản ứng và tương quan âm tính với các xét nghiệm chức năng phổi như dung tích sống gắng sức và khả năng khuếch tán cho cacbon monoxide (DLCO). Ở bệnh nhân xơ cứng bì hệ thống da lan rộng (dcSSc), Hsp90 tương quan dương tính với thang điểm da Rodnan được sửa đổi. Ở bệnh nhân SSc-ILD được điều trị bằng cyclophosphamide, không thấy sự khác biệt về Hsp90 giữa lúc bắt đầu và sau 1, 6, hoặc 12 tháng điều trị. Tuy nhiên, Hsp90 ban đầu có thể dự đoán sự thay đổi DLCO sau 12 tháng. Nghiên cứu này chỉ ra rằng nồng độ Hsp90 trong huyết tương gia tăng ở bệnh nhân SSc so với nhóm đối chứng khỏe mạnh cùng độ tuổi và giới tính. Hsp90 gia tăng ở bệnh nhân SSc có liên quan với hoạt động viêm gia tăng, chức năng phổi kém hơn và trong dcSSc, với mức độ tổn thương da. Hsp90 trong huyết tương ban đầu có thể dự đoán sự thay đổi DLCO sau 12 tháng ở bệnh nhân SSc-ILD điều trị bằng cyclophosphamide.

Community detection is often used to understand the structure of large and complex networks. One of the most popular algorithms for uncovering community structure is the so-called Louvain algorithm. We show that this algorithm has a major defect that largely went unnoticed until now: the Louvain algorithm may yield arbitrarily badly connected communities. In the worst case, communities may even be disconnected, especially when running the algorithm iteratively. In our experimental analysis, we observe that up to 25% of the communities are badly connected and up to 16% are disconnected. To address this problem, we introduce the Leiden algorithm. We prove that the Leiden algorithm yields communities that are guaranteed to be connected. In addition, we prove that, when the Leiden algorithm is applied iteratively, it converges to a partition in which all subsets of all communities are locally optimally assigned. Furthermore, by relying on a fast local move approach, the Leiden algorithm runs faster than the Louvain algorithm. We demonstrate the performance of the Leiden algorithm for several benchmark and real-world networks. We find that the Leiden algorithm is faster than the Louvain algorithm and uncovers better partitions, in addition to providing explicit guarantees.

Microkinetic analyses of aqueous electrochemistry involving gaseous H₂or O₂, i.e., hydrogen evolution reaction (HER), hydrogen oxidation reaction (HOR), oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), are revisited. The Tafel slopes used to evaluate the rate determining steps generally assume extreme coverage of the adsorbed species (θ ≈ 0 or ≈1), although, in practice, the slopes are coverage-dependent. We conducted detailed kinetic analyses describing the coverage-dependent Tafel slopes for the aforementioned reactions. Our careful analyses provide a general benchmark for experimentally observed Tafel slopes that can be assigned to specific rate determining steps. The Tafel analysis is a powerful tool for discussing the rate determining steps involved in electrocatalysis, but our study also demonstrated that overly simplified assumptions led to an inaccurate description of the surface electrocatalysis. Additionally, in many studies, Tafel analyses have been performed in conjunction with the Butler-Volmer equation, where its applicability regarding only electron transfer kinetics is often overlooked. Based on the derived kinetic description of the HER/HOR as an example, the limitation of Butler-Volmer expression in electrocatalysis is also discussed in this report.

Alzheimer’s disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.