bluuebunny/crossref_metadata_2025 huggingface dataset:
The history of sexual selection research provides insights as to why females are still understudied
Authors: Ah-King Malin
Published: November 2022

While it is widely acknowledged that Darwin’s descriptions of females were gender-biased, gender bias in current sexual selection research is less recognized. An examination of the history of sexual selection research shows prevalent male precedence—that research starts with male-centered investigations or explanations and thereafter includes female-centered equivalents. In comparison, the incidence of female precedence is low. Furthermore, a comparison between the volume of publications focusing on sexual selection in males versus in females shows that the former far outnumber the latter. This bias is not only a historical pattern; sexual selection theory and research are still male-centered—due to conspicuous traits, practical obstacles, and continued gender bias. Even the way sexual selection is commonly defined contributes to this bias. This history provides an illustrative example by which we can learn to recognize biases and identify gaps in knowledge. I conclude with a call for the scientific community to interrogate its own biases and suggest strategies for alleviating biases in this field and beyond.
Cryo-EM structure of the agonist-bound Hsp90-XAP2-AHR cytosolic complex
Authors: Gruszczyk Jakub , Grandvuillemin Loïc , Lai-Kee-Him Josephine , Paloni Matteo , Savva Christos G. , Germain Pierre , Grimaldi Marina , Boulahtouf Abdelhay , Kwong Hok-Sau , Bous Julien , Ancelin Aurélie , Bechara Cherine , Barducci Alessandro , Balaguer Patrick , Bourguet William
Published: November 2022

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates a broad spectrum of (patho)physiological processes in response to numerous substances including pollutants, natural products and metabolites. However, the scarcity of structural data precludes understanding of how AHR is activated by such diverse compounds. Our 2.85 Å structure of the human indirubin-bound AHR complex with the chaperone Hsp90 and the co-chaperone XAP2, reported herein, reveals a closed conformation Hsp90 dimer with AHR threaded through its lumen and XAP2 serving as a brace. Importantly, we disclose the long-awaited structure of the AHR PAS-B domain revealing a unique organisation of the ligand-binding pocket and the structural determinants of ligand-binding specificity and promiscuity of the receptor. By providing structural details of the molecular initiating event leading to AHR activation, our study rationalises almost forty years of biochemical data and provides a framework for future mechanistic studies and structure-guided drug design.
First-in-human phase Ia study of the PI3Kα inhibitor CYH33 in patients with solid tumors
Authors: Wei Xiao-Li , Liu Fu-Rong , Liu Ji-Hong , Zhao Hong-Yun , Zhang Yang , Wang Zhi-Qiang , Qiu Miao-Zhen , Xu Fei , Yu Qiu-Qiong , Du Yi-Wu , Shi Yan-Xia , Wang De-Sheng , Wang Feng-Hua , Xu Rui-Hua
Published: November 2022

PIK3CA mutations are highly prevalent in solid tumors. Targeting phosphatidylinositol 3-kinase α is therefore an attractive strategy for treating cancers harboring PIK3CA mutations. Here, we report the results from a phase Ia, open label, dose-escalation and -expansion study (NCT03544905) of CYH33, a highly selective PI3Kα inhibitor, in advanced solid tumors. The primary outcomes were the safety, tolerability, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of CYH33. The secondary outcomes included evaluation of pharmacokinetics, preliminary efficacy and changes in pharmacodynamic biomarkers in response to CYH33 treatment. The exploratory outcome was the relationship between the efficacy of CYH33 treatment and tumor biomarker status, including PIK3CA mutations. A total of 51 patients (19 in the dose escalation stage and 32 in the dose expansion stage) including 36 (70.6%) patients (4 in the dose escalation stage and 32 in the dose expansion stage) with PIK3CA mutations received CYH33 1–60 mg. The MTD of CYH33 was 40 mg once daily, which was also selected as the RP2D. The most common grade 3/4 treatment-related adverse events were hyperglycemia, rash, platelet count decreased, peripheral edema, and fatigue. Forty-two out of 51 patients were evaluable for response, the confirmed objective response rate was 11.9% (5/42). Among 36 patients harboring PIK3CA mutations, 28 patients were evaluable for response, the confirmed objective response rate was 14.3% (4/28). In conclusion, CYH33 exhibits a manageable safety profile and preliminary anti-tumor efficacy in solid tumors harboring PIK3CA mutations.
Breaking through water-splitting bottlenecks over carbon nitride with fluorination
Authors: Wu Ji , Liu Zhonghuan , Lin Xinyu , Jiang Enhui , Zhang Shuai , Huo Pengwei , Yan Yan , Zhou Peng , Yan Yongsheng
Published: November 2022

Graphitic carbon nitride has long been considered incapable of splitting water molecules into hydrogen and oxygen without adding small molecule organics despite the fact that the visible-light response and proper band structure fulfills the proper energy requirements to evolve oxygen. Herein, through in-situ observations of a collective C = O bonding, we identify the long-hidden bottleneck of photocatalytic overall water splitting on a single-phased g-C3N4 catalyst via fluorination. As carbon sites are occupied with surface fluorine atoms, intermediate C=O bonding is vastly minimized on the surface and an order-of-magnitude improved H2 evolution rate compared to the pristine g-C3N4 catalyst and continuous O2 evolution is achieved. Density functional theory calculations suggest an optimized oxygen evolution reaction pathway on neighboring N atoms by C–F interaction, which effectively avoids the excessively strong C-O interaction or weak N-O interaction on the pristine g-C3N4.
A global dynamic runoff application and dataset based on the assimilation of GPM, SMAP, and GCN250 curve number datasets
Authors: Sujud Lara H. , Jaafar Hadi H.
Published: November 2022

Runoff modelling is a crucial element in hydrologic sciences. However, a global runoff database is not currently available at a resolution higher than 0.1°. We use the recently developed Global Curve Number dataset (GCN250) to develop a dynamic runoff application (2015 – present) and that can be accessed via a Google Earth Engine application. We also provide a global mean monthly runoff dataset for April 2015-2021 in GeoTIFF format at a 250-meter resolution. We utilize soil moisture and GPM rainfall to dynamically retrieve the appropriate curve number and generate the corresponding runoff anywhere on Earth. Mean annual global runoff ratio results for 2021 were comparable to the runoff ratio from the Global Land Data Assimilation System (0.079 vs. 0.077, respectively). Mean annual global runoff from GCN and GLDAS were within 11% each other for 2020–2021 (0.18 vs. 0.16 mm/day, respectively). The GCN250 runoff application and the dataset are useful for many water applications such hydrologic design, land management, water resources management, and flood risk assessment.
Evaluating different web applications to assess the toxicity of plasticizers
Authors: Arulanandam Charli Deepak , Hwang Jiang-Shiou , Rathinam Arthur James , Dahms Hans-Uwe
Published: November 2022

Plasticizers increase the flexibility of plastics. As environmental leachates they lead to increased water and soil pollution, as well as to serious harm to human health. This study was set out to explore various web applications to predict the toxicological properties of plasticizers. Web-based tools (e.g., BOILED-Egg, LAZAR, PROTOX-II, CarcinoPred-EL) and VEGA were accessed via an 5th–10th generation computer in order to obtain toxicological predictions. Based on the LAZAR mutagenicity assessment was only bisphenol F predicted as mutagenic. The BBP and DBP in RF; DEHP in RF and XGBoost; DNOP in RF and XGBoost models were predicted as carcinogenic in the CarcinoPred-EL web application. From the bee predictive model (KNN/IRFMN) BPF, di-n-propyl phthalate, diallyl phthalate, dibutyl phthalate, and diisohexyl phthalate were predicted as strong bee toxicants. Acute toxicity for fish using the model Sarpy/IRFMN predicted 19 plasticizers as strong toxicants with LC50 values of less than 1 mg/L. This study also considered plasticizer effects on gastrointestinal absorption and other toxicological endpoints.
A Bayesian generative neural network framework for epidemic inference problems
Authors: Biazzo Indaco , Braunstein Alfredo , Dall’Asta Luca , Mazza Fabio
Published: November 2022

The reconstruction of missing information in epidemic spreading on contact networks can be essential in the prevention and containment strategies. The identification and warning of infectious but asymptomatic individuals (i.e., contact tracing), the well-known patient-zero problem, or the inference of the infectivity values in structured populations are examples of significant epidemic inference problems. As the number of possible epidemic cascades grows exponentially with the number of individuals involved and only an almost negligible subset of them is compatible with the observations (e.g., medical tests), epidemic inference in contact networks poses incredible computational challenges. We present a new generative neural networks framework that learns to generate the most probable infection cascades compatible with observations. The proposed method achieves better (in some cases, significantly better) or comparable results with existing methods in all problems considered both in synthetic and real contact networks. Given its generality, clear Bayesian and variational nature, the presented framework paves the way to solve fundamental inference epidemic problems with high precision in small and medium-sized real case scenarios such as the spread of infections in workplaces and hospitals.
Robustness and efficiency of international pesticide trade networks subject to link removal strategies
Authors: Xie Wen-Jie , Li Jian-An , Wei Na , Wang Li , Zhou Wei-Xing
Published: November 2022

The international pesticide trade network (iPTN) is a key factor affecting global food production and food security. The trade relationship is a key component in iPTNs. In a complex international trade environment, we model the impacts of uncertain factors such as trade wars, economic blockades and local wars, as removing vital relationships in the trade network. There are many complex network studies on node centrality, but few on link centrality or link importance. We propose a new method for computing network link centrality. The main innovation of the method is in converting the original network into a dual graph, the nodes in the dual graph corresponding to the links of the original network. Through the dual graph, the node centrality indicators can measure the centrality of the links in the original network. We verify the effectiveness of the network link centrality indicator based on the dual graph in the iPTN, analyze the relationship between the existing network link centrality indicators and the indicator proposed in this paper, and compare their differences. It is found that the trade relationships with larger indicators (hub, outcloseness, outdegree) based on the dual graph have a greater impact on network efficiency than those based on the original pesticide trade networks.
Differential effects of periodontal microbiome on the rheumatoid factor induction during rheumatoid arthritis pathogenesis
Authors: Kim Ji-Won , Jung Hyerin , Baek In-Pyo , Nam Yoojun , Kang Jaewoo , Chung Min Kyung , Park Jun-Beom , Lee Jennifer , Kwok Seung-Ki , Kim Wan-Uk , Park Sung-Hwan , Ju Ji Hyeon
Published: November 2022

Association between exposure to periodontal bacteria and development of autoantibodies related to rheumatoid arthritis (RA) has been widely accepted; however, direct causal relationship between periodontal bacteria and rheumatoid factor (RF) is currently not fully understood. We investigated whether periodontal bacteria could affect RF status. Patients with preclinical, new-onset, or chronic RA underwent periodontal examination, and investigation of subgingival microbiome via 16S rRNA sequencing. Degree of arthritis and RF induction was examined in collagen-induced arthritis (CIA) mice that were orally inoculated with different periodontal bacteria species. Subsequently, single-cell RNA sequencing analysis of the mouse spleen cells was performed. Patients with preclinical RA showed an increased abundance of the Porphyromonadacae family in the subgingival microbiome compared to those with new-onset or chronic RA, despite comparable periodontitis severity among them. Notably, a distinct subgingival microbial community was found between patients with high-positive RF and those with negative or low-positive RF (p=0.022). Oral infections with the periodontal pathogensP. gingivalisandTreponema denticolain CIA mice similarly enhanced arthritis score, but resulted in different levels of RF induction. Genes related to B cell receptor signaling, B cell proliferation, activation, and differentiation, and CD4+T cell costimulation and cytokine production were involved in the differential induction of RF in mice exposed to different bacteria. In summary, periodontal microbiome might shape RF status by affecting the humoral immune response during RA pathogenesis.
λ-Carrageenan promotes plant growth in banana via enhancement of cellular metabolism, nutrient uptake, and cellular homeostasis
Authors: Thye Kah-Lok , Wan Abdullah Wan Muhamad Asrul Nizam , Balia Yusof Zetty Norhana , Wee Chien-Yeong , Ong-Abdullah Janna , Loh Jiun-Yan , Cheng Wan-Hee , Lamasudin Dhilia Udie , Lai Kok-Song
Published: November 2022

Banana (Musa acuminata) is an important fruit crop and source of income for various countries, including Malaysia. To date, current agrochemical practice has become a disputable issue due to its detrimental effect on the environment. λ-carrageenan, a natural polysaccharide extracted from edible red seaweed, has been claimed to be a potential plant growth stimulator. Hence, the present study investigates the effects of λ-carrageenan on plant growth using Musa acuminata cv. Berangan (AAA). Vegetative growth such as plant height, root length, pseudostem diameter, and fresh weight was improved significantly in λ-carrageenan-treated banana plants at an optimum concentration of 750 ppm. Enhancement of root structure was also observed in optimum λ-carrageenan treatment, facilitating nutrients uptake in banana plants. Further biochemical assays and gene expression analysis revealed that the increment in growth performance was consistent with the increase of chlorophyll content, protein content, and phenolic content, suggesting that λ-carrageenan increases photosynthesis rate, protein biosynthesis, and secondary metabolites biosynthesis which eventually stimulate growth. Besides, λ-carrageenan at optimum concentration also increased catalase and peroxidase activities, which led to a significant reduction in hydrogen peroxide and malondialdehyde, maintaining cellular homeostasis in banana plants. Altogether, λ-carrageenan at optimum concentration improves the growth of banana plants via inducing metabolic processes, enhancing nutrient uptake, and regulation of cell homeostasis. Further investigations are needed to evaluate the effectiveness of λ-carrageenan on banana plants under field conditions.
DFT analogue of prospecting the spin-polarised properties of layered perovskites Ba2ErNbO6 and Ba2TmNbO6 influenced by electronic structure
Authors: Khandy Saveer Ahmad , Gupta Dinesh C.
Published: November 2022

Since the unexpected accelerated discovery of half-metallic perovskites is continuously on the rise both from basic sciences and application-oriented sides. Herein, for the first time in this carried research work, we significantly delivered a detailed analysis on one of experimentally synthesized perovskite structure Ba2ErNbO6 and in related to Ba2TmNbO6 within the realm of unified density functional theory. Initially, the structural stability of two molecular perovskite structures were critically established interms of their total ground state and cohesive energies by the expendition of Brich Murnaghan equation of state. Also, the tolerance factor (τ) oversees the cubic structural stability without possessing any geometrical strains. More likely, the density functional perturbation theory (DFPT) has been calibrated to perceive the dynamical context of these layered structures. Also, from the understandings of second order elastic and mechanical parameters adresses their suitable ductile characteristics. The quantum mechanical refinement of their intrinsic electronic structures were systematically tuned by the exploitation of Generalised gradient approximation (GGA), on-site Hubbard scheme (GGA + U) selected to the strongly correlated electrons of particular angular momentum and modified Becke-Johnson (mBJ) potential. Moreover, the two-dimensional representation of asymmetric density of states (DOS) pinned around the Fermi-level (EF) and the interpretation linked to their corresponding spin-polarised band structures signatures the well-known half-metallic nature. Subsequently, the transport properties especially the value of figure of merit (ZT) equals to unity (1) along the selected chemical potential range at different temperatures. The summed-up properties and the overall tendency triggers the possibility of these materials to register their extending applications in spintronics, thermoelectrics, nanoengineering, and radioisotope generator perspectives.
The study of aggression and affiliation motifs in bottlenose dolphins’ social networks
Authors: Pérez-Manrique Ana , Fernández-Gracia Juan , Gomila Antoni , Ramasco José J.
Published: November 2022

Networks in biology have provided a powerful tool to describe and study very complex biological processes and systems such as animal societies. Social network analysis allows us to assess different processes occurring in animal groups. In the current study, we use this approach to investigate how conflict dynamics and post-conflict interactions shape the social networks of groups of captive bottlenose dolphins. We first examined temporal changes and aggression-affiliation motifs in the observed dolphins’ network structure. Using the results of the previous analysis, we built two models that simulate the dynamics of aggression and affiliation in a small dolphin group. The first model is based only on the observed statistics of interactions, whereas the second includes post conflict memory effects as well. We found that the resulting social networks and their most common motifs matched the association patterns observed in wild and captive dolphins. Furthermore, the model with memory was able to capture the observed dynamics of this group of dolphins. Thus, our models suggest the presence and influence of post-conflict behaviors on the structure of captive dolphins’ social networks. Therefore, the network approach reveals as an effective method to define animal social networks and study animal sociality. Finally, this approach can have important applications in the management of animal populations in captive settings.
Cyclododecane shaping, sublimation rate and residue analysis for the extraction of painting micro-samples from resin cross-sections
Authors: Jaques Victory Armida Janine , Zikmundová Eva , Holas Jiří , Zikmund Tomáš , Kaiser Jozef , Holcová Katarína
Published: November 2022

Cross-section preparation of painting micro-samples is part of their routine analysis. This type of preparation can be used for several analytical techniques, such as scanning electron microscopy, Fourier-transform infrared spectroscopy, Raman spectroscopy, and optical microscopy. These techniques offer high-resolution imaging and/or elemental information, providing access to technical and material data important for the interpretation, preservation, and restoration of painted artworks. However, it also means that the material from the sample embedded in the resin becomes unreachable for further analysis, except for the polished surface of the cross-section. Degradation of the embedding medium can also occur over time, which can lead to misinterpretation, loss of information, or even complete destruction of the embedded sample. In the field of cultural heritage, cyclododecane (CDD) is commonly used for the consolidation and protection of objects, and is used in the preparation of cross-sections to prevent contamination of the sample by the embedding medium. This study enhanced the existing preparation process by shaping the CDD layer to enable extraction of the micro-sample from the resin if needed, without compromising the integrity of the sample. Moreover, the purity, the sublimation rate in a normal environment and a vacuum, and the impact of CDD on three different types of samples (historical painting on a canvas, wall painting fragment, model sample) were examined.
Development of a deep learning method for improving diagnostic accuracy for uterine sarcoma cases
Authors: Toyohara Yusuke , Sone Kenbun , Noda Katsuhiko , Yoshida Kaname , Kurokawa Ryo , Tanishima Tomoya , Kato Shimpei , Inui Shohei , Nakai Yudai , Ishida Masanori , Gonoi Wataru , Tanimoto Saki , Takahashi Yu , Inoue Futaba , Kukita Asako , Kawata Yoshiko , Taguchi Ayumi , Furusawa Akiko , Miyamoto Yuichiro , Tsukazaki Takehiro , Tanikawa Michihiro , Iriyama Takayuki , Mori-Uchino Mayuyo , Tsuruga Tetsushi , Oda Katsutoshi , Yasugi Toshiharu , Takechi Kimihiro , Abe Osamu , Osuga Yutaka
Published: November 2022

Uterine sarcomas have very poor prognoses and are sometimes difficult to distinguish from uterine leiomyomas on preoperative examinations. Herein, we investigated whether deep neural network (DNN) models can improve the accuracy of preoperative MRI-based diagnosis in patients with uterine sarcomas. Fifteen sequences of MRI for patients (uterine sarcoma group: n = 63; uterine leiomyoma: n = 200) were used to train the models. Six radiologists (three specialists, three practitioners) interpreted the same images for validation. The most important individual sequences for diagnosis were axial T2-weighted imaging (T2WI), sagittal T2WI, and diffusion-weighted imaging. These sequences also represented the most accurate combination (accuracy: 91.3%), achieving diagnostic ability comparable to that of specialists (accuracy: 88.3%) and superior to that of practitioners (accuracy: 80.1%). Moreover, radiologists’ diagnostic accuracy improved when provided with DNN results (specialists: 89.6%; practitioners: 92.3%). Our DNN models are valuable to improve diagnostic accuracy, especially in filling the gap of clinical skills between interpreters. This method can be a universal model for the use of deep learning in the diagnostic imaging of rare tumors.
The effects of visitors and social isolation from a peer on the behavior of a mixed-species pair of captive gibbons
Authors: Lee Saein , Ryu Heungjin , Yi Yoonjung , Jang Seon-a , Gye Haeun , Choi Ahyun , Cho Haeun , Lee Bae-keun , Choe Jae C.
Published: November 2022

Human visitors affect the behavior of captive animals, which is the so-called visitor effect. The number and behavior of visitors may influence stress-related behaviors in captive animals, such as self-scratching, yawning, and visitor-directed vigilance. A social group setting can be applied to alleviate such negative visitor effects and facilitate social behavior and interactions between individuals. In this study, we examined how the number and behavior of visitors are related to stress-related behaviors of a captive mixed-species gibbon pair comprising a yellow-cheek gibbon (Nomascus gabriellae) and a white-handed gibbon (Hylobates lar). The two gibbons were separated during the study period, and we examined whether the social isolation stimulated the visitor effect. The frequency of stress-related behaviors of the gibbons increased and the social playing between them decreased proportionally to visitor number. In the indoor enclosure, the gibbons increased their visitor-directed vigilance when visitors shouted or struck the glass partition. Our findings indicate that the number and behavior of visitors negatively affect captive gibbons and that a mixed-species social setting can help gibbons reduce visitor-induced stress. Future studies with larger sample sizes will improve the understanding of the visitor effect and the social setting in the captivity.
Prediction of monthly dry days with machine learning algorithms: a case study in Northern Bangladesh
Authors: Osmani Shabbir Ahmed , Kim Jong-Suk , Jun Changhyun , Sumon Md. Wahiduzzaman , Baik Jongjin , Lee Jinwook
Published: November 2022

Dry days at varied scale are an important topic in climate discussions. Prolonged dry days define a dry period. Dry days with a specific rainfall threshold may visualize a climate scenario of a locality. The variation of monthly dry days from station to station could be correlated with several climatic factors. This study suggests a novel approach for predicting monthly dry days (MDD) of six target stations using different machine learning (ML) algorithms in Bangladesh. Several rainfall thresholds were used to prepare the datasets of monthly dry days (MDD) and monthly wet days (MWD). A group of ML algorithms, like Bagged Trees (BT), Exponential Gaussian Process Regression (EGPR), Matern Gaussian Process Regression (MGPR), Linear Support Vector Machine (LSVM), Fine Trees (FT) and Linear Regression (LR) were evaluated on building a competitive prediction model of MDD. In validation of the study, EGPR-based models were able to better capture the monthly dry days (MDD) over Bangladesh compared to those by MGPR, LSVM, BT, LR and FT-based models. When MDD were the predictors for all six target stations, EGPR produced highest meanR2of 0.91 (min. 0.89 and max. 0.92) with a least meanRMSEof 2.14 (min. 1.78 and max. 2.69) compared to other models. An explicit evaluation of the ML algorithms using one-year lead time approach demonstrated that BT and EGPR were the most result-oriented algorithms (R2 = 0.78 for both models). However, having a leastRMSE,EGPR was chosen as the best model in one year lead time. The dataset of monthly dry–wet days was the best predictor in the lead-time approach. In addition, sensitivity analysis demonstrated sensitivity of each station on the prediction of MDD of target stations. Monte Carlo simulation was introduced to assess the robustness of the developed models. EGPR model declared its robustness up to certain limit of randomness on the testing data. The output of this study can be referred to the agricultural sector to mitigate the impacts of dry spells on agriculture.
Investigating subtle changes in facial expression to assess acute pain in Japanese macaques
Authors: Gris Vanessa N. , Broche Nelson , Kaneko Akihisa , Okamoto Munehiro , Suzuki Juri , Mills Daniel S. , Miyabe-Nishiwaki Takako
Published: November 2022

Changes in facial expression provide cues for assessing emotional states in mammals and may provide non-verbal signals of pain. This study uses geometric morphometrics (GMM) to explore the facial shape variation in female Japanese macaques who underwent experimental laparotomy. Face image samples were collected from video footage of fourteen macaques before surgery and 1, 3, and 7 days after the procedure. Image samples in the pre-surgical condition were considered pain-free, and facial expressions emerging after surgery were investigated as potential indicators of pain. Landmarks for shape analysis were selected based on the underlying facial musculature and their corresponding facial action units and then annotated in 324 pre-surgical and 750 post-surgical images. The expression of pain is likely to vary between individuals. Tightly closed eyelids or squeezed eyes and lip tension were the most commonly observed facial changes on day 1 after surgery (p < 0.01974). A good overall inter-rater reliability [ICC = 0.99 (95% CI 0.75–1.0)] was observed with the method. The study emphasizes the importance of individualized assessment and provides a better understanding of facial cues to pain for captive macaque care.
Preliminary results of the cross-sectional associations of sedentary behavior and physical activity with serum brain-derived neurotrophic factor in adults with coronary heart disease
Authors: Ullrich Antje , Wenzel Kristin , Bahls Martin , Voigt Lisa , Könemann Stephanie , Dörr Marcus , Wurm Susanne , Ulbricht Sabina
Published: November 2022

This is the first study to analyze the association of accelerometer-measured patterns of habitual physical activity (PA) and sedentary behavior (SB) with serum BDNF in individuals with coronary heart disease. A total of 30 individuals (M = 69.5 years; 80% men) participated in this pre-post study that aimed to test a multi-behavioral intervention. All participants underwent standardized measurement of anthropometric variables, blood collection, self-administered survey, and accelerometer-based measurement of PA and SB over seven days. Serum BDNF concentrations were measured using enzyme-linked immunosorbent assay kit. We applied separate multiple linear regression analysis to estimate the associations of baseline SB pattern measures, light and moderate-to-vigorous PA with serum BDNF (n = 29). Participants spent 508.7 ± 76.5 min/d in SB, 258.5 ± 71.2 min/d in light PA, and 21.2 ± 15.2 min/d in moderate-to-vigorous PA. Per day, individuals had 15.5 ± 3.2 numbers of 10-to-30 min bouts of SB (average length: 22.2 ± 2.1 min) and 3.4 ± 1.2 numbers of > 30 min bouts of SB (average length: 43.8 ± 2.4 min). Regression analysis revealed no significant associations between any of the accelerometer-based measures and serum BDNF. The findings of this study did not reveal an association of accelerometer-measured PA and SB pattern variables with serum BDNF in individuals with coronary heart disease. In addition, our data revealed a considerable variation of PA and SB which should be considered in future studies.
Mating experiences with the same partner enhanced mating activities of naïve male medaka fish
Authors: Daimon Masahiro , Katsumura Takafumi , Sakamoto Hirotaka , Ansai Satoshi , Takeuchi Hideaki
Published: November 2022

Mating experience shapes male mating behavior across species, from insects, fish, and birds, to rodents. Here, we investigated the effect of multiple mating experiences on male mating behavior in “naïve” (defined as sexually inexperienced) male medaka fish. The latency to mate with the same female partner significantly decreased after the second encounter, whereas when the partner was changed, the latency to mate was not decreased. These findings suggest that mating experiences enhanced the mating activity of naïve males for the familiar female, but not for an unfamiliar female. In contrast, the mating experiences of “experienced” (defined as those having mated > 7 times) males with the same partner did not influence their latency to mate. Furthermore, we identified 10 highly and differentially expressed genes in the brains of the naïve males after the mating experience and revealed 3 genes that are required for a functional cascade of the thyroid hormone system. Together, these findings suggest that the mating experience of naïve male medaka fish influences their mating behaviors, with neural changes triggered by thyroid hormone activation in the brain.
Allyl ether of mansonone G as a potential anticancer agent for colorectal cancer
Authors: Chanvijit Savinee , Phuagkhaopong Suttinee , Mahalapbutr Panupong , Klaewkla Methus , Chavasiri Warinthorn , Wonganan Piyanuch
Published: November 2022

Mansonone G (MG), a 1,2-naphthoquinone isolated from the heartwood of Mansonia gagei Drumm, exhibited several pharmacological activities such as anti-bacterial, anti-estrogenic and anti-adipogenic effect. This study evaluated the cytotoxicity of MG and its derivatives as well as determined the mechanism(s) underlying the cytotoxic activity of the most potent MG derivative on two CRC cell lines, HCT-116 cells carrying p53 wild-type and HT-29 cells carrying p53 mutant. We found that MG and its derivatives could inhibit viability of HCT-116 and HT-29 cells in a concentration-dependent manner. Of all semi-synthetic derivatives of MG, allyl ether mansonone G (MG7) was the most potent cytotoxic agent toward cancer cells and less toxic to normal cells. MG7 could induce ROS generation which was associated with cytotoxicity and apoptosis in both HCT-116 and HT-29 cells. Western blot analysis revealed that MG7 downregulated the expression of Bcl-2 and Bcl-xL proteins in both CRC cell lines and upregulated the expression of BAK protein in HT-29 cells. Moreover, MG7 inhibited AKT signaling pathway in both CRC cell lines and modulated ERK1/2 signaling pathway by inhibiting ERK1/2 phosphorylation in HCT-116 cells and activating ERK1/2 phosphorylation in HT-29 cells. Molecular docking revealed that MG7 could bind to the ATP-binding pocket of AKT and ERK1 via hydrophobic interactions.
Interplay of different synchronization modes and synaptic plasticity in a system of class I neurons
Authors: Ratas Irmantas , Pyragas Kestutis
Published: November 2022

We analyze the effect of spike-timing-dependent plasticity (STDP) on a system of pulse-coupled class I neurons. Our research begins with a system of two mutually connected quadratic integrate-and-fire (QIF) neurons, which are canonical representatives of class I neurons. Along with various asymptotic modes previously observed in other neuronal models with plastic synapses, we found a stable synchronous mode characterized by unidirectional link from a slower neuron to a faster neuron. In this frequency-locked mode, the faster neuron emits multiple spikes per cycle of the slower neuron. We analytically obtain the Arnold tongues for this mode without STDP and with STDP. We also consider larger plastic networks of QIF neurons and show that the detected mode can manifest itself in such a way that slow neurons become pacemakers. As a result, slow and fast neurons can form large synchronous clusters that generate low-frequency oscillations. We demonstrate the generality of the results obtained with two connected QIF neurons using Wang–Buzsáki and Morris–Lecar biophysically plausible class I neuron models.
Dietary shredded steam-exploded pine particle supplementation as a strategy to mitigate chronic cyclic heat stress by modulating gut microbiota in broilers
Authors: Goel Akshat , Ncho Chris Major , Kim Beom-June , Jeong Chae-Mi , Gupta Vaishali , Jung Ji-Young , Ha Si-Young , Yang Jae-Kyung , Choi Yang-Ho
Published: November 2022

Improving the availability of underutilized waste for the economic use of livestock feed can be important in countries where feed grain production is scarce. Modulating the gut microbiota through the fibrous content present in these wastes may help mitigate the adverse effects of heat stress (HS). Here, we investigated the effects of dietary steam-exploded pine particle (SPP), a value-added waste product, on the performance, gut health, and cecum microbiota in heat-stressed broilers. Ross 308 broilers (n = 180) at 29 days of age were distributed into three dietary treatment groups (0%, 1%, and 2% SPP) and two temperature conditions (NT: 21 °C; CHS: 31 °C) and grown for seven days. CHS, but not SPP, adversely affected performance parameters, but SPP did not interactively modulate these results. On the contrary, both differently affected other parameters. CHS resulted in increased rectal temperature, total protein in serum, and Nox4 gene expression, whereas 2% SPP increased GLP-2 and the Nox4 gene expression in the duodenum in comparison to 0% and 1% SPP. CHS significantly modified the beta-diversity of cecal microbiota while 1% SPP supplementation in diets increased the abundance of the favorable bacterial genera in chicken. Concludingly, CHS adversely affects growth performances, gut health, stress-related genes, and cecal microbiota while dietary 1% SPP may facilitate the proliferation of beneficial microorganisms in the cecum of broilers.
Influence of tramadol on bacterial burden in the standard neutropenic thigh infection model
Authors: Rox K.
Published: November 2022

The neutropenic thigh infection model is one of the standard models in pharmacokinetic/ pharmacodynamic (PK/PD) characterization of novel antibacterials which are urgently needed due to the rise of antimicrobial resistance. The model enables to investigate PK/PD parameters crucial for translation of animal results towards humans. However, the neutropenic thigh infection model can result in moderate to severe discomfort of the animals, especially when high inocula are used. Tramadol has been proven to reduce pain effectively. This study investigates if tramadol influences the bacterial burden in the primary organ, the thighs, and organs affected by secondary seeding. Therefore, several strains of the ESKAPE pathogens, namely S. aureus, P. aeruginosa, K. pneumoniae, E. coli, A. baumannii and E. faecalis were examined. It was shown that tramadol did not influence the bacterial burden neither in thighs nor in organs affected by secondary seeding for the strains of E. faecalis, S. aureus, P. aeruginosa, K. pneumoniae and E.coli tested here, whereas secondary seeding seemed to be affected by tramadol for the tested strain of A. baumannii. Consequently, it was demonstrated that tramadol is an option to reduce discomfort in the untreated group for the strains of five out of the six tested ESKAPE pathogens and, thereby, contributes to the refinement of one of the standard PK/PD models.
A tissue attached to self-expandable metal stents for biliary stricture could be useful to find malignancy
Authors: Kwon Hyungjun , Jung Min Kyu , Park Sung Jin , Heo Jun , Lee Dong Wook , Kang Yoo Na , Han Jaryung , Han Young Seok , Lee Won Kee
Published: November 2022

Biliary strictures can have several benign or malignant causes. We attempted to determine the usefulness of establishing a diagnosis using self-expandable metal stents (SEMS) in a prospective series of patients with suspected malignant biliary obstruction. Data of patients who underwent SEMS removal from August 2016 to December 2019 were collected. During this period, 55 patients underwent endobiliary biopsy and SEMS insertion and removal. Fifty-five consecutive patients (mean age, 69 years; range 53–90 years) were enrolled, and of these, 37 were male and 18 were female. A final diagnosis was established using biopsy specimens in 37 cases (67.3%) and surgical specimens in 6 cases (10.9%), with 12 cases (21.8%) diagnosed on radiological follow-up. The final diagnoses included malignancy in 34 cases (61.8%) and benign stricture in 21 cases (38.2%). Endobiliary biopsy had a sensitivity and specificity of 44.1% and 95.2%, whereas SEMS cytology had a sensitivity and specificity of 52.9% and 100%, respectively. Combining endobiliary biopsy and/or SEMS cytology yielded a sensitivity and specificity of 73.5% and 95.2%, respectively. (1) The use of biopsy results alone as a diagnostic tool yielded an area under the receiver operating characteristic curve (AUC) of 0.70 (0.60–0.79). (2) The addition of SEMS to the biopsy results yielded an AUC of 0.86 (0.78–0.94). (3) The addition of CA 19–9 levels to the biopsy results yielded an AUC of 0.81 (0.71–0.94). (4) Combining the endobiliary biopsy results, SEMS tissues, and CA 19–9 levels yielded the best diagnostic accuracy, with an AUC of 0.90 (0.83–0.98). Detection of biliary obstruction using the combination strategy was better than the diagnostic results based on biopsy alone according to recent 3-year data. Our study suggested that SEMS removal could help establish a diagnosis of suspected malignant biliary obstruction.
Targeting arginase-1 exerts antitumor effects in multiple myeloma and mitigates bortezomib-induced cardiotoxicity
Authors: Ramji Kavita , Grzywa Tomasz M. , Sosnowska Anna , Paterek Aleksandra , Okninska Marta , Pilch Zofia , Barankiewicz Joanna , Garbicz Filip , Borg Katarzyna , Bany-Laszewicz Urszula , Zerrouqi Abdesamad , Pyrzynska Beata , Rodziewicz-Lurzynska Anna , Papiernik Diana , Sklepkiewicz Piotr , Kedzierska Hanna , Staruch Adam , Sadowski Radoslaw , Ciepiela Olga , Lech-Maranda Ewa , Juszczynski Przemyslaw , Mackiewicz Urszula , Maczewski Michal , Nowis Dominika , Golab Jakub
Published: November 2022

Multiple myeloma (MM) remains an incurable malignancy of plasma cells despite constantly evolving therapeutic approaches including various types of immunotherapy. Increased arginase activity has been associated with potent suppression of T-cell immune responses in different types of cancer. Here, we investigated the role of arginase 1 (ARG1) in Vκ*MYC model of MM in mice. ARG1 expression in myeloid cells correlated with tumor progression and was accompanied by a systemic drop in ʟ-arginine levels. In MM-bearing mice antigen-induced proliferation of adoptively transferred T-cells was strongly suppressed and T-cell proliferation was restored by pharmacological arginase inhibition. Progression of Vκ*MYC tumors was significantly delayed in mice with myeloid-specific ARG1 deletion. Arginase inhibition effectively inhibited tumor progression although it failed to augment anti-myeloma effects of bortezomib. However, arginase inhibitor completely prevented development of bortezomib-induced cardiotoxicity in mice. Altogether, these findings indicate that arginase inhibitors could be further tested as a complementary strategy in multiple myeloma to mitigate adverse cardiac events without compromising antitumor efficacy of proteasome inhibitors.
ABE8e adenine base editor precisely and efficiently corrects a recurrent COL7A1 nonsense mutation
Authors: Sheriff Adam , Guri Ina , Zebrowska Paulina , Llopis-Hernandez Virginia , Brooks Imogen R. , Tekkela Stavroula , Subramaniam Kavita , Gebrezgabher Ruta , Naso Gaetano , Petrova Anastasia , Balon Katarzyna , Onoufriadis Alexandros , Kujawa Dorota , Kotulska Martyna , Newby Gregory , Łaczmański Łukasz , Liu David R. , McGrath John A. , Jacków Joanna
Published: November 2022

Base editing introduces precise single-nucleotide edits in genomic DNA and has the potential to treat genetic diseases such as the blistering skin disease recessive dystrophic epidermolysis bullosa (RDEB), which is characterized by mutations in the COL7A1 gene and type VII collagen (C7) deficiency. Adenine base editors (ABEs) convert A-T base pairs to G-C base pairs without requiring double-stranded DNA breaks or donor DNA templates. Here, we use ABE8e, a recently evolved ABE, to correct primary RDEB patient fibroblasts harboring the recurrent RDEB nonsense mutation c.5047 C > T (p.Arg1683Ter) in exon 54 of COL7A1 and use a next generation sequencing workflow to interrogate post-treatment outcomes. Electroporation of ABE8e mRNA into a bulk population of RDEB patient fibroblasts resulted in remarkably efficient (94.6%) correction of the pathogenic allele, restoring COL7A1 mRNA and expression of C7 protein in western blots and in 3D skin constructs. Off-target DNA analysis did not detect off-target editing in treated patient-derived fibroblasts and there was no detectable increase in A-to-I changes in the RNA. Taken together, we have established a highly efficient pipeline for gene correction in primary fibroblasts with a favorable safety profile. This work lays a foundation for developing therapies for RDEB patients using ex vivo or in vivo base editing strategies.
Diverse cloud and aerosol impacts on solar photovoltaic potential in southern China and northern India
Authors: Yang Jiangyan , Yi Bingqi , Wang Shuai , Liu Yushan , Li Yuxiao
Published: November 2022

Cloud and aerosol are two important modulators that influence the solar radiation reaching the earth’s surface. It is intriguing to find diverse impacts of clouds and aerosols over Southern China (SC) and Northern India (NI) which result in remarkable differences in the plane-of-array irradiance (POAI) that signifies the maximum available solar photovoltaic potential by combining the latest satellite retrieval results and modeling tools. By separating the impacts of cloud and aerosol on the POAI, it is found that clouds are responsible for the most reduction of POAI in the SC, while aerosols and clouds are equally important for the NI region. The frequent occurrences of low and middle level clouds with high optical depth in the SC, as compared with the much lower occurrences of all levels of clouds with lower optical depth in the NI, is regarded as the major reason for the differences in the POAI. The differences in the main compositions of aerosols in the SC (sulfate) and the NI (dust) could be essential to answer the question of why higher aerosol optical depth in the SC whereas leads to weaker reduction in the POAI than that in the NI. The mitigation measures targeting on the controls of different types of aerosols should be considered for different regions.
Regulation of protein and oxidative energy metabolism are down-regulated in the skeletal muscles of Asiatic black bears during hibernation
Authors: Miyazaki Mitsunori , Shimozuru Michito , Kitaoka Yu , Takahashi Kenya , Tsubota Toshio
Published: November 2022

Hibernating animals exhibit an unexplained physiological characteristic of skeletal muscles being atrophy resistance, in which case muscle mass and strength remain almost unchanged both before and after hibernation. In this study, we examined the alterations in the regulatory systems of protein and energy metabolism in the skeletal muscles of Asiatic black bears during hibernation. Skeletal muscle samples (vastus lateralis muscle) were collected from identical individuals (n = 8) during the active (July) and hibernating (February) periods, while histochemical and biochemical analyses were performed. We observed no significant alterations in body weight, muscle fiber size, and fiber type composition during the active and hibernating periods, indicating that the skeletal muscles of bears are very well preserved during hibernation. In hibernating bear skeletal muscles, both regulatory pathways of muscle protein synthesis (Akt/mechanistic target of rapamycin and mitogen-activated protein kinase systems) and proteolysis (ubiquitin–proteasome and autophagy systems) were down-regulated. Gene expression levels of factors regulating oxidative metabolism were also decreased in hibernating bear skeletal muscles. This is likely an adaptive strategy to minimize the energy wasting of amino acids and lipids during hibernation, which is accompanied by a prolonged period of disuse and starvation.
A diagnostic accuracy study on an innovative auto-edge detection technique for identifying simulated implant fractures on radiographic images
Authors: Khosravifard Negar , Saberi Bardia Vadiati , Khosravifard Amir , Zakerjafari Hamidreza , Vafaei Reihaneh , Ghaffari Mohammad Ebrahim
Published: November 2022

Implant fracture is a rare but devastating complication of treatment in partially or fully edentulous patients which requires prompt diagnosis. Nevertheless, studies on defining the most accurate technique for the detection of implant fractures are lacking. In the present study, the Canny edge detection algorithm was applied on multiple radiographic modalities including parallel periapical (PPA), oblique periapical (OPA), and cone beam CT (CBCT) with and without metal artifact reduction (MAR) to examine its accuracy for diagnosis of simulated implant fractures. Radiographs were taken from 24 intact implants and 24 implants with artificially created fractures. Images were evaluated in their original and Canny formats. The accuracy of each radiograph was assessed by comparison with a reference standard of direct observation of the implant. The greatest area under the receiver operating characteristic curve belonged to Canny CBCT with MAR (0.958), followed by original CBCT with MAR (0.917), original CBCT without MAR = Canny CBCT without MAR = Canny OPA (0.875), Canny PPA (0.833), original PPA = original OPA (0.792), respectively. The Canny edge detection algorithm is suggested as an innovative method for accurate diagnosis of clinically suspected implant fractures on CBCT and periapical radiographies.