bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole transcriptome and proteome analyses identify potential targets and mechanisms underlying tumor treating fields against glioblastoma
Authors: Xu Shengchao , Luo Chengke , Chen Dikang , Tang Lu , Chen Ling , Liu Zhixiong
Published: August 2022

Glioblastoma (GBM) is one of the most malignant types of brain cancer. Tumor treating fields (TTFields) is the up-to-date treatment for GBM. However, its molecular mechanism requires additional investigation. Herein, a novel TTFields system was developed (CL-301A) and its efficiency in suppressing GBM cell proliferation and inducing cell apoptosis was demonstrated. Through the whole proteomic and transcriptomic analyses, a multitude of differentially expressed proteins (1243), mRNAs (4191), miRtNAs (47), lncRNAs (4286), and circRNAs (13,903) were identified. Bioinformatic analysis indicated that TTFields mainly affected nuclear proteins and interrupt cell mitosis-related events. Moreover, the inhibition of autophagy could significantly enhance the anti-GBM activity of TTFields. And CDK2-AS1 might be a target of TTFields to mediate cell cycle arrest via regulating CDK2 mRNA stability. This study provided valuable resources for understanding the mechanism of TTFields, which might further assist the investigation of TTFields in GBM treatment.
Multiomics characterization implicates PTK7 in ovarian cancer EMT and cell plasticity and offers strategies for therapeutic intervention
Authors: Raivola Juuli , Dini Alice , Karvonen Hanna , Piki Emilia , Salokas Kari , Niininen Wilhelmiina , Kaleva Laura , Zhang Kaiyang , Arjama Mariliina , Gudoityte Greta , Seashore-Ludlow Brinton , Varjosalo Markku , Kallioniemi Olli , Hautaniemi Sampsa , Murumägi Astrid , Ungureanu Daniela
Published: August 2022

Most patients with ovarian cancer (OC) are diagnosed at a late stage when there are very few therapeutic options and a poor prognosis. This is due to the lack of clearly defined underlying mechanisms or an oncogenic addiction that can be targeted pharmacologically, unlike other types of cancer. Here, we identified protein tyrosine kinase 7 (PTK7) as a potential new therapeutic target in OC following a multiomics approach using genetic and pharmacological interventions. We performed proteomics analyses upon PTK7 knockdown in OC cells and identified novel downstream effectors such as synuclein-γ (SNCG), SALL2, and PP1γ, and these findings were corroborated in ex vivo primary samples using PTK7 monoclonal antibody cofetuzumab. Our phosphoproteomics analyses demonstrated that PTK7 modulates cell adhesion and Rho-GTPase signaling to sustain epithelial-mesenchymal transition (EMT) and cell plasticity, which was confirmed by high-content image analysis of 3D models. Furthermore, using high-throughput drug sensitivity testing (525 drugs) we show that targeting PTK7 exhibited synergistic activity with chemotherapeutic agent paclitaxel, CHK1/2 inhibitor prexasertib, and PLK1 inhibitor GSK461364, among others, in OC cells and ex vivo primary samples. Taken together, our study provides unique insight into the function of PTK7, which helps to define its role in mediating aberrant Wnt signaling in ovarian cancer.
Rubisco forms a lattice inside alpha-carboxysomes
Authors: Metskas Lauren Ann , Ortega Davi , Oltrogge Luke M. , Blikstad Cecilia , Lovejoy Derik R. , Laughlin Thomas G. , Savage David F. , Jensen Grant J.
Published: August 2022

Despite the importance of microcompartments in prokaryotic biology and bioengineering, structural heterogeneity has prevented a complete understanding of their architecture, ultrastructure, and spatial organization. Here, we employ cryo-electron tomography to image α-carboxysomes, a pseudo-icosahedral microcompartment responsible for carbon fixation. We have solved a high-resolution subtomogram average of the Rubisco cargo inside the carboxysome, and determined the arrangement of the enzyme. We find that the H. neapolitanus Rubisco polymerizes in vivo, mediated by the small Rubisco subunit. These fibrils can further pack to form a lattice with six-fold pseudo-symmetry. This arrangement preserves freedom of motion and accessibility around the Rubisco active site and the binding sites for two other carboxysome proteins, CsoSCA (a carbonic anhydrase) and the disordered CsoS2, even at Rubisco concentrations exceeding 800 μM. This characterization of Rubisco cargo inside the α-carboxysome provides insight into the balance between order and disorder in microcompartment organization.
Surface interfacial analysis of simulant high level nuclear waste glass dissolved in synthetic cement solutions
Authors: Corkhill Claire L. , Mann Colleen , Eskelsen Jeremy R. , Leonard Donovan N. , Mottram Lucy M. , Stennett Martin C. , Ayling Jennifer M. S. , Thorpe Clare L. , Cole Max R. , Nicholas Sarah , Tappero Ryan , Pierce Eric M.
Published: August 2022

The corrosion mechanisms and kinetics of a Mg-rich alkali aluminoborosilicate glass simulating UK high-level waste (CaZn28) were investigated upon dissolution in synthetic cement solutions. Dissolution varied as a function the different pH and alkali/alkaline earth content of each cement solution. High resolution microscopy and spectroscopy techniques ascertained the nature of the interface between the glass and the cement solutions. TEM-EDS revealed alkali- and alkaline earth-rich silica gels, into which K, Ca and Mg were incorporated. TEM-SAED, combined with synchrotron micro-focus XRD, identified the ubiquitous precipitation of the Mg-aluminate layered double hydroxide phase, meixnerite (Mg6Al2(OH)18·4H2O), in addition to goethite (FeOOH) and crystalline silica. The C-S-H phase, tobermorite (Ca5Si6O16(OH)2·4H2O), was identified in the most Ca-rich solution only. These data give insight to the role of alkali/alkaline earth-rich solutions in the dissolution or radioactive waste glasses, of importance to the final disposition in a geological disposal facility.
Erythroid lineage-specific lentiviral RNAi vectors suitable for molecular functional studies and therapeutic applications
Authors: Bagchi Abhirup , Devaraju Nivedhitha , Chambayil Karthik , Rajendiran Vignesh , Venkatesan Vigneshwaran , Sayed Nilofer , Pai Aswin Anand , Nath Aneesha , David Ernest , Nakamura Yukio , Balasubramanian Poonkuzhali , Srivastava Alok , Thangavel Saravanabhavan , Mohankumar Kumarasamypet M. , Velayudhan Shaji R.
Published: August 2022

Numerous genes exert multifaceted roles in hematopoiesis. Therefore, we generated novel lineage-specific RNA interference (RNAi) lentiviral vectors, H23B-Ery-Lin-shRNA and H234B-Ery-Lin-shRNA, to probe the functions of these genes in erythroid cells without affecting other hematopoietic lineages. The lineage specificity of these vectors was confirmed by transducing multiple hematopoietic cells to express a fluorescent protein. Unlike the previously reported erythroid lineage RNAi vector, our vectors were designed for cloning the short hairpin RNAs (shRNAs) for any gene, and they also provide superior knockdown of the target gene expression with a single shRNA integration per cell. High-level lineage-specific downregulation of BCL11A and ZBTB7A, two well-characterized transcriptional repressors of HBG in adult erythroid cells, was achieved with substantial induction of fetal hemoglobin with a single-copy lentiviral vector integration. Transduction of primary healthy donor CD34+ cells with these vectors resulted in >80% reduction in the target protein levels and up to 40% elevation in the γ-chain levels in the differentiated erythroid cells. Xenotransplantation of the human CD34+ cells transduced with H23B-Ery-Lin-shBCL11A LV in immunocompromised mice showed ~ 60% reduction in BCL11A protein expression with ~ 40% elevation of γ-chain levels in the erythroid cells derived from the transduced CD34+ cells. Overall, the novel erythroid lineage-specific lentiviral RNAi vectors described in this study provide a high-level knockdown of target gene expression in the erythroid cells, making them suitable for their use in gene therapy for hemoglobinopathies. Additionally, the design of these vectors also makes them ideal for high-throughput RNAi screening for studying normal and pathological erythropoiesis.
PTPRD and CNTNAP2 as markers of tumor aggressiveness in oligodendrogliomas
Authors: Rautajoki Kirsi J. , Jaatinen Serafiina , Tiihonen Aliisa M. , Annala Matti , Vuorinen Elisa M. , Kivinen Anni , Rauhala Minna J. , Maass Kendra K. , Pajtler Kristian W. , Yli-Harja Olli , Helén Pauli , Haapasalo Joonas , Haapasalo Hannu , Zhang Wei , Nykter Matti
Published: August 2022

Oligodendrogliomas are typically associated with the most favorable prognosis among diffuse gliomas. However, many of the tumors progress, eventually leading to patient death. To characterize the changes associated with oligodendroglioma recurrence and progression, we analyzed two recurrent oligodendroglioma tumors upon diagnosis and after tumor relapse based on whole-genome and RNA sequencing. Relapsed tumors were diagnosed as glioblastomas with an oligodendroglioma component before the World Health Organization classification update in 2016. Both patients died within 12 months after relapse. One patient carried an inactivating POLE mutation leading to a clearly hypermutated progressed tumor. Strikingly, both relapsed tumors carried focal chromosomal rearrangements in PTPRD and CNTNAP2 genes with associated decreased gene expression. TP53 mutation was also detected in both patients after tumor relapse. In The Cancer Genome Atlas (TCGA) diffuse glioma cohort, PTPRD and CNTNAP2 expression decreased by tumor grade in oligodendrogliomas and PTPRD expression also in IDH-mutant astrocytomas. Low expression of the genes was associated with poor overall survival. Our analysis provides information about aggressive oligodendrogliomas with worse prognosis and suggests that PTPRD and CNTNAP2 expression could represent an informative marker for their stratification.
Visuo-spatial attention deficit in children with reading difficulties
Authors: Franceschini Sandro , Bertoni Sara , Puccio Giovanna , Gori Simone , Termine Cristiano , Facoetti Andrea
Published: August 2022

Although developmental reading disorders (developmental dyslexia) have been mainly associated with auditory-phonological deficits, recent longitudinal and training studies have shown a possible causal role of visuo-attentional skills in reading acquisition. Indeed, visuo-attentional mechanisms could be involved in the orthographic processing of the letter string and the graphemic parsing that precede the grapheme-to-phoneme mapping. Here, we used a simple paper-and-pencil task composed of three labyrinths to measure visuo-spatial attention in a large sample of primary school children (n = 398). In comparison to visual search tasks requiring visual working memory, our labyrinth task mainly measures distributed and focused visuo-spatial attention, also controlling for sensorimotor learning. Compared to typical readers (n = 340), children with reading difficulties (n = 58) showed clear visuo-spatial attention impairments that appear not linked to motor coordination and procedural learning skills implicated in this paper and pencil task. Since visual attention is dysfunctional in about 40% of the children with reading difficulties, an efficient reading remediation program should integrate both auditory-phonological and visuo-attentional interventions.
Estimation of model accuracy by a unique set of features and tree-based regressor
Authors: Bitton Mor , Keasar Chen
Published: August 2022

Computationally generated models of protein structures bridge the gap between the practically negligible price tag of sequencing and the high cost of experimental structure determination. By providing a low-cost (and often free) partial alternative to experimentally determined structures, these models help biologists design and interpret their experiments. Obviously, the more accurate the models the more useful they are. However, methods for protein structure prediction generate many structural models of various qualities, necessitating means for the estimation of their accuracy. In this work we present MESHI_consensus, a new method for the estimation of model accuracy. The method uses a tree-based regressor and a set of structural, target-based, and consensus-based features. The new method achieved high performance in the EMA (Estimation of Model Accuracy) track of the recent CASP14 community-wide experiment (https://predictioncenter.org/casp14/index.cgi). The tertiary structure prediction track of that experiment revealed an unprecedented leap in prediction performance by a single prediction group/method, namely AlphaFold2. This achievement would inevitably have a profound impact on the field of protein structure prediction, including the accuracy estimation sub-task. We conclude this manuscript with some speculations regarding the future role of accuracy estimation in a new era of accurate protein structure prediction.
A non-randomized, open-label study of the safety and effectiveness of a novel non-pneumatic compression device (NPCD) for lower limb lymphedema
Authors: Rockson Stanley G. , Karaca-Mandic Pinar , Nguyen Michelle , Shadduck Kristin , Gingerich Phyllis , Campione Elizabeth , Hetrrick Heather
Published: August 2022

Lower extremity lymphedema (LEL) can result in detriments to quality of life (QOL) and impose a significant economic burden on patients and payers. A common component of treatment is pneumatic compression, which requires patients to remain immobile. We investigated a novel non-pneumatic compression device (NPCD) that allows patients to remain active during compression treatment, to see if it reduces swelling and improves QOL. We conducted a non-randomized, open-label, 12-week pilot study of adult patients with primary or secondary unilateral LEL, and measured changes in limb edema and QOL using the Lymphedema Quality of Life Questionnaire (LYMQOL). Twenty-four subjects were enrolled; the majority were female (17) with secondary lymphedema (21). Eighteen completed the study. Statistically significant improvements were observed in overall QOL, aggregated LYMQOL total score, and three of four LYMQOL subscales (Function, Appearance, Mood). The fourth (Symptoms) trended toward significant improvement (p = 0.06). The average reduction in affected limb edema was 39.4%. The novel NPCD produced statistically significant improvements in QOL, functioning, and edema volume of patients with LEL. Innovations in devices to manage LEL can be effective while allowing patients to maintain mobility and physical activity during treatment.
Hygienic assessment of fish handling practices along production and supply chain and its public health implications in Central Oromia, Ethiopia
Authors: Bedane Tesfaye D. , Agga Getahun E. , Gutema Fanta D.
Published: August 2022

Fishborne diseases are among the major causes of morbidity and mortality worldwide. Contamination of the aquatic ecosystem and unhygienic handling practices along the fish supply chain can lead to a contaminated fish. Consumption of raw or under cooked fish and fish products is a major source of fishborne infections in humans. Despite reports of fish contamination with foodborne pathogens in Ethiopia, information regarding the hygienic status of fish handling practices is limited. We assessed fish hygienic handling practices at production sites and along the fish supply chain in three towns in east Shewa zone of Oromia. Data were collected using a semi-structured questionnaire interviews and personal observations. The study consisted of purposively selected respondents comprising of 50 fishermen, 10 retailers, 20 food establishments serving fish, and 120 consumers. Descriptive statistics and Chi-square test were used to present the proportion of various actors along the fish production and supply chain and to compare the proportions of observations among the different categories respectively. We observed that the lakes were accessible to animals and exposed to chemical and microbial contaminations through rainwater run-off. Fish were processed under unhygienic practices like washing of filleted fish with lake water, indiscriminate processing at unhygienic landing sites, use of a single knife for processing all fish with infrequent washing and with no disinfection in between. Majority (70%; n = 10) of the retailers and all the food establishments transported fish in vehicles with no cold chain facilities. Good hygienic practices we observed were the use of refrigerators for storage in all retailers and 70% (n = 20) of the food establishments; 30% of retailers used vehicles with a cold chain facility for the transportation of fish. Over three-fourths (77%; n = 120) of the consumers preferred consuming raw fish; 80% of them lacked the knowledge of fishborne diseases. The study revealed a wide range of unhygienic handling practices along fish production and supply chain; lack of infrastructure for post-harvest fish handling and processing, lack of appropriate transportation facilities and presence of knowledge gaps regarding fish borne diseases.
Prediction of sex-determination mechanisms in avian primordial germ cells using RNA-seq analysis
Authors: Ichikawa Kennosuke , Nakamura Yoshiaki , Bono Hidemasa , Ezaki Ryo , Matsuzaki Mei , Horiuchi Hiroyuki
Published: August 2022

In birds, sex is determined through cell-autonomous mechanisms and various factors, such as the dosage of DMRT1. While the sex-determination mechanism in gonads is well known, the mechanism in germ cells remains unclear. In this study, we explored the gene expression profiles of male and female primordial germ cells (PGCs) during embryogenesis in chickens to predict the mechanism underlying sex determination. Male and female PGCs were isolated from blood and gonads with a purity > 96% using flow cytometry and analyzed using RNA-seq. Prior to settlement in the gonads, female circulating PGCs (cPGCs) obtained from blood displayed sex-biased expression. Gonadal PGCs (gPGCs) also exhibited sex-biased expression, and the number of female-biased genes detected was higher than that of male-biased genes. The female-biased genes in gPGCs were enriched in some metabolic processes. To reveal the mechanisms underlying the transcriptional regulation of female-biased genes in gPGCs, we performed stimulation tests. Retinoic acid stimulation of cultured gPGCs derived from male embryos resulted in the upregulation of several female-biased genes. Overall, our results suggest that sex determination in avian PGCs involves aspects of both cell-autonomous and somatic-cell regulation. Moreover, it appears that sex determination occurs earlier in females than in males.
The effect of reinforcement on the mechanical properties of veneered wood fiber/polypropylene composites assembled with chlorinated polypropylene
Authors: Liu Yinan , Chen Feng , Ni Xiaohui , Xia Xinghua
Published: August 2022

Wood fiber/polypropylene (WF/PP) composites are environmentally friendly materials with high dimensional stability and mechanical properties. However, the applications of WF/PP composites are limited by an unattractive surface texture. In this study, the WF/PP composites were decorated with poplar wood veneer using chlorinated polypropylene (CPP) as a hot melt adhesive, the bonding strength is over 1.18 MPa. Surface bonding strength tests and scanning electron microscopy (SEM) were performed to analyze the quality of the CPP bonding layer. The physical and mechanical properties of the veneered WF/PP boards and unveneered controls were examined to determine the effects of reinforcement. The result shows that after veneered the tension strength and modulus of the whole composite board were increased over 30% and 10%; the flexural strength and modulus were increased over 10% and 20%. Low-velocity impact testing was performed to determine the impact resistance properties of the composites. Higher ratios of wood fiber in the WF/PP composite led to a higher surface bonding strength, which was evident in the SEM images. Wood veneer decoration increased the mechanical strength of the whole composite board. A tighter bond along the CPP layer would provide additional reinforcement of the veneered composite’s mechanical properties.
Transcriptome analysis of halophyte Nitraria tangutorum reveals multiple mechanisms to enhance salt resistance
Authors: Wang Lirong , Du Meng , Wang Bo , Duan Huirong , Zhang Benyin , Wang Dong , Li Yi , Wang Jiuli
Published: August 2022

As a typical halophyte, Nitraria tangutorum Bobr. has attracted the interest of many researchers with the excellent salt tolerance. Elucidation of the mechanism of N. tangutorum salinity tolerance will facilitate the genetic improvement of productive plants faced with salinity. To reveal the molecular response to gradually accumulated salt stress in N. tangutorum, RNA-sequencing and analysis of gradually accumulated NaCl treated samples and control samples were performed, and a total of 1419 differentially expressed genes were identified, including 949 down-regulated genes and 470 up-regulated genes. Detailed analysis uncovered that the catabolism of organic compounds mainly based on oxidative phosphorylation genes was up-regulated. Additionally, various antioxidant genes, especially anthocyanin-related genes, were found to help N. tangutorum remove reactive oxygen species. Moreover, the Mitogen activated protein kinase signaling pathway and other signaling pathways co-regulated various salt tolerance activities. Additionally, intracellular ion homeostasis was maintained via regulation of osmotic regulator-related genes, cutin-related genes, and cell elongation-related genes to retain cellular water and reduce ion concentration. In particularly, simultaneous up-regulation in cytoskeleton-related genes, cell wall-related genes, and auxin-related genes, provided evidence of important role of cell expansion in plant salt tolerance. In conclusion, complex regulatory mechanisms modulated by multiple genes might contribute to the salt tolerance by N. tangutorum.
Predictors of psychological stress and behavioural diversity among captive red panda in Indian zoos and their implications for global captive management
Authors: Sohel Khan Aamer , Lea Stephen E. G. , Chand Piar , Rai Upashna , Baskaran Nagarajan
Published: August 2022

At high elevations, biodiversity is at elevated risk from extinctions due to rapid environmental changes. In the most of its range in Himalayas, the red panda, an endangered species, is struggling to survive in the wild, and a global captive breeding programme has been launched to conserve the species. Because captivity can have negative impacts on animals, reducing the chance of successful reintroduction, we investigated the predictors of stereotyped behaviour and behavioural diversity of red panda (n = 26), and the effect of stereotypy on their behavioural diversity in three Indian zoos. Multivariate analysis showed that stereotypy increased with density of logs on the ground, age and higher among pandas in zoo 3 compared to zoo 2, but decreased with number of nests, sociality, tree density and tree height used. Similarly, behavioural diversity increased with log density, but decreased among pandas in zoo 2 compared to zoo 1, during summer compared to winter, and also with ambient temperature, stereotypy, tree density, and tree height used. The relationship between stereotypy and behavioural diversity was negative, but not significant. Provision of a greater density of trees was associated with higher levels of daytime inactivity. Findings from this study have global relevance, as the captive red panda experiences similar welfare issues around the world, and our data provide empirical support for some existing guidelines for red panda husbandry.
Reliability and accuracy of dental MRI for measuring root canal length of incisors and canines: a clinical pilot study
Authors: Zidan Mousa , Schwindling Franz S. , Juerchott Alexander , Mente Johannes , Nittka Mathias , Hosseini Zahra , Heiland Sabine , Bendszus Martin , Hilgenfeld Tim
Published: August 2022

To evaluate whether high-resolution, non-contrast-enhanced dental MRI (dMRI) can reliably and accurately measure the canal length of incisors and canines compared with cone-beam computed tomography (CBCT). Three-Tesla dMRI was performed in 31 participants (mean age: 50.1 ± 14.2 years) with CBCT data. In total, 67 teeth were included (28 from the upper jaw and 39 from the lower jaw; 25 central incisors, 22 lateral incisors, and 20 canines). CBCT and dMRI datasets were reconstructed to visualize the root canal pathway in a single slice in the vestibulo-oral (V-O) and mesio-distal (M-D) direction. Root canal length was measured twice by two radiologists using dMRI and CBCT. Data were statistically analyzed by calculating intraclass correlation coefficients (ICCs) and performing Bland–Altman analysis. The reliability of dMRI measurements was excellent and comparable to that of CBCT measurements (intra-rater I/intra-rater II/inter-rater was 0.990/0.965/0.951 for dMRI vs. 0.990/0.994/0.992 for CBCT in the M-D direction and 0.991/0.956/0.967 for dMRI vs. 0.998/0.994/0.996 for CBCT in the V-O direction). According to Bland–Altman analysis, the mean (95% confidence interval) underestimation of root canal lengths was 0.67 mm (− 1.22 to 2.57) for dMRI and 0.87 mm (− 0.29 to 2.04) for CBCT in the M-D direction/V-O direction. In 92.5% of cases, dMRI measurements of canal length had an accuracy within 0–2 mm. Visualization and measurement of canal length in vivo using dMRI is feasible. The reliability of dMRI measurements was high and comparable to that of CBCT measurements. However, the spatial and temporal resolution of dMRI is lower than that of CBCT, which means dMRI measurements are less accurate than CBCT measurements. This means dMRI is currently unsuitable for measuring canal length in clinical practice.
Genomic data is missing for many highly invasive species, restricting our preparedness for escalating incursion rates
Authors: Matheson Paige , McGaughran Angela
Published: August 2022

Biological invasions drive environmental change, potentially threatening native biodiversity, human health, and global economies. Population genomics is an increasingly popular tool in invasion biology, improving accuracy and providing new insights into the genetic factors that underpin invasion success compared to research based on a small number of genetic loci. We examine the extent to which population genomic resources, including reference genomes, have been used or are available for invasive species research. We find that 82% of species on the International Union for Conservation of Nature “100 Worst Invasive Alien Species” list have been studied using some form of population genetic data, but just 32% of these species have been studied using population genomic data. Further, 55% of the list’s species lack a reference genome. With incursion rates escalating globally, understanding how genome-driven processes facilitate invasion is critical, but despite a promising trend of increasing uptake, “invasion genomics” is still in its infancy. We discuss how population genomic data can enhance our understanding of biological invasion and inform proactive detection and management of invasive species, and we call for more research that specifically targets this area.
Song recordings suggest feeding ground sharing in Southern Hemisphere humpback whales
Authors: Schall Elena , Djokic Divna , Ross-Marsh Erin C. , Oña Javier , Denkinger Judith , Ernesto Baumgarten Julio , Rodrigues Padovese Linilson , Rossi-Santos Marcos R. , Carvalho Gonçalves Maria Isabel , Sousa-Lima Renata , Hucke-Gaete Rodrigo , Elwen Simon , Buchan Susannah , Gridley Tess , Van Opzeeland Ilse
Published: August 2022

The Atlantic sector of the Southern Ocean (ASSO) has one of the highest densities of Antarctic krill (Euphausia superba) compared to other polar and subpolar regions, which attracts migratory baleen whale species to aggregate in this area for feeding. Humpback whales (Megaptera novaeangliae) also sing extensively while on the Southern Ocean feeding grounds which allows for the exploration of song similarity between feeding grounds and breeding populations which helps to understand population mixing. The results of comparative song analyses between the ASSO and the Ecuadorian and Brazilian breeding populations and recordings from the Chilean, South African and Namibian migration routes/mid-latitude feeding grounds revealed that individuals from at least three humpback whale breeding populations most likely migrate to shared feeding grounds in the ASSO. Humpback whales from different populations potentially mix at different times (i.e., years) at feeding hotspots in variable locations. The ASSO seems to provide sufficient prey resources and seems to present an important area for both cultural and maybe even genetic exchange between populations supporting the maintenance of large gene pools. Assuming that multi-population feeding hotspots are also suitable habitat for krill and other krill-dependent predators, these areas in the ASSO should be carefully managed integrating population, ecosystem and fisheries management.
Cell death responses to acute high light mediated by non-photochemical quenching in the dinoflagellate Karenia brevis
Authors: Gao Yida , Erdner Deana L.
Published: August 2022

Programmed cell death (PCD) can be induced in microalgae by many abiotic challenges via generation of reactive oxygen species (ROS). Marine phytoplankton live in a highly variable light environment, yet the potential for excess photosynthetically available radiation to trigger PCD has not been examined. On the other hand, photoprotective non-photochemical quenching (NPQ) is hypothesized to counteract intracellular ROS, potentially preventing cell death. The main objective of this study is to investigate high-light-induced death processes and their relationship with photosynthesis in bloom-forming dinoflagellate Karenia brevis. Here, we characterized the prevalence of ROS, caspase-like enzyme activity and cell death as well as photosynthetic status under acute irradiance of 500, 750 or 1000 µmol m−2 s−1. PCD only occurred at the largest light shift. Although depressed photosynthetic capacities and oxidative stress were apparent across the stress gradient, they did not necessarily lead to cell death. NPQ exhibited dose-dependent activation with increasing light stress, which enabled cells to resist or delay PCD. These results highlight the important role of the balance between ROS generation and NPQ activation on determining cell fates in Karenia under acute irradiance stress. This research also provides insights into potential survival strategies and mechanisms of cell loss under a changeable light environment.
Jitter noise modeling and its removal using recursive least squares in shape from focus systems
Authors: Mutahira Husna , Shin Vladimir , Park Unsang , Muhammad Mannan Saeed
Published: August 2022

Three-dimensional shape recovery from the set of 2D images has many applications in computer vision and related fields. Passive techniques of 3D shape recovery utilize a single view point and one of these techniques is Shape from Focus or SFF. In SFF systems, a stack of images is taken with a single camera by manipulating its focus settings. During the image acquisition, the inter-frame distance or the sampling step size is predetermined and assumed constant. However, in a practical situation, this step size cannot remain constant due to mechanical vibrations of the translational stage, causing jitter. This jitter produces Jitter noise in the resulting focus curves. Jitter noise is invisible in every image, because all images in the stack are exposed to the same error in focus; thus, limiting the use of traditional noise removal techniques. This manuscript formulates a model of Jitter noise based on Quadratic function and the Taylor series. The proposed method, then, solves the jittering problem for SFF systems through recursive least squares (RLS) filtering. Different noise levels were considered during experiments performed on both real as well as simulated objects. A new metric measure is also proposed, referred to as depth distortion (DD), which calculates the number of pixels contributing to the RMSE in percentage. The proposed measure is used along with the RMSE and correlation, to compute and test the reconstructed shape quality. The results confirm the effectiveness of the proposed scheme.
A lignan from Alnus japonica inhibits glioblastoma tumorspheres by suppression of FOXM1
Authors: Shim Jin-Kyoung , Lim Seung Hoon , Jeong Ji Hye , Choi Ran Joo , Oh Yoojung , Park Junseong , Choi Sunghee , Hong Junpyo , Kim Seo Jin , Moon Ju Hyung , Kim Eui Hyun , Teo Wan-Yee , Park Bong Jin , Chang Jong Hee , Ryu Jae-Ha , Kang Seok-Gu
Published: August 2022

Forkhead Box M1 (FOXM1) is known to regulate cell proliferation, apoptosis and tumorigenesis. The lignan, (−)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol (DFS), from Alnus japonica has shown anti-cancer effects against colon cancer cells by suppressing FOXM1. The present study hypothesized that DFS can have anti-cancer effects against glioblastoma (GBM) tumorspheres (TSs). Immunoprecipitation and luciferase reporter assays were performed to evaluate the ability of DFS to suppress nuclear translocation of β-catenin through β-catenin/FOXM1 binding. DFS-pretreated GBM TSs were evaluated to assess the ability of DFS to inhibit GBM TSs and their transcriptional profiles. The in vivo efficacy was examined in orthotopic xenograft models of GBM. Expression of FOXM1 was higher in GBM than in normal tissues. DFS-induced FOXM1 protein degradation blocked β-catenin translocation into the nucleus and consequently suppressed downstream target genes of FOXM1 pathways. DFS inhibited cell viability and ATP levels, while increasing apoptosis, and it reduced tumorsphere formation and the invasiveness of GBM TSs. And DFS reduced the activities of transcription factors related to tumorigenesis, stemness, and invasiveness. DFS significantly inhibited tumor growth and prolonged the survival rate of mice in orthotopic xenograft models of GBM. It suggests that DFS inhibits the proliferation of GBM TSs by suppressing FOXM1. DFS may be a potential therapeutic agent to treat GBM.
New fossils from Kromdraai and Drimolen, South Africa, and their distinctiveness among Paranthropus robustus
Authors: Braga José , Chinamatira G. , Zipfel B. , Zimmer V.
Published: August 2022

Most fossil hominin species are sampled with spatial, temporal or anatomical biases that can hinder assessments of their paleodiversity, and may not yield genuine evolutionary signals. We use new fossils from the Kromdraai (Unit P) and Drimolen sites (South Africa) to provide insights into the paleodiversity of the Lower Pleistocene robust australopith, Paranthropus robustus. Our focus is the morphology of the temporal bone and the relationships between size and shape (allometry) of the semi-circular canals (SCC), an aspect that has not yet been investigated among southern African australopiths. We find significant size and shape SCC differences between P. robustus from Kromdraai, Drimolen and Swartkrans. This site-related variation is consistent with other differences observed on the temporal bone. P. robustus from Kromdraai Unit P is distinctive because of its smaller temporal bone and SCC, and its proportionally less developed posterior SCC, independently of age and sex. We emphasize the importance of allometry to interpret paleodiversity in P. robustus as either the consequence of differences in body size, or as yet unknown factors. Some features of the inner ear of P. robustus represent directional selection soon after its origin, whereas the size and shape variations described here may result from evolutionary changes.
Preliminary study of thermal density distribution and entropy analysis during cycling exercise stress test using infrared thermography
Authors: Bogomilsky S. , Hoffer O. , Shalmon G. , Scheinowitz M.
Published: August 2022

Considerable differences related to the results of temperature changes acquired during exercise exist, and in many cases, these lead to poor correlation with physiological variables. In this preliminary study we investigated the temperature changes and the temperature distribution (entropy) of the torso during a graded cycling exercise stress test using thermal imaging and studied the correlation between the increase in pulmonary ventilation (VE) and the changes in the surface temperature of the anterior torso during exercise. Thermal images of the anterior torso were captured every 30 s during the exercise, while the resistance was gradually increased every minute until exhaustion. The thermal images were processed to obtain a mean temperature in the regions of interest (ROI) (chest, forehead, and abdomen). We also developed an algorithm to calculate the distribution of temperature and texture (entropy) within each ROI. No changes were found in absolute temperatures. However, the entropy of the chest surface area increased significantly throughout the exercise test, compared with baseline temperature at rest. This increase in entropy was significantly correlated with exercise duration and intensity (p < 0.001). Furthermore, a high correlation between the increase in VE and chest entropy during exercise was detected (r = 0.9515). No correlations were found between the increase in entropy and the abdomen or the forehead compared with the VE. The non-invasive IR thermal imaging during graded exercise, combined with advanced image processing, successfully correlates surface thermography with exercise duration and pulmonary ventilation.
A comparison of reinforcement learning models of human spatial navigation
Authors: He Qiliang , Liu Jancy Ling , Eschapasse Lou , Beveridge Elizabeth H. , Brown Thackery I.
Published: August 2022

Reinforcement learning (RL) models have been influential in characterizing human learning and decision making, but few studies apply them to characterizing human spatial navigation and even fewer systematically compare RL models under different navigation requirements. Because RL can characterize one’s learning strategies quantitatively and in a continuous manner, and one’s consistency of using such strategies, it can provide a novel and important perspective for understanding the marked individual differences in human navigation and disentangle navigation strategies from navigation performance. One-hundred and fourteen participants completed wayfinding tasks in a virtual environment where different phases manipulated navigation requirements. We compared performance of five RL models (3 model-free, 1 model-based and 1 “hybrid”) at fitting navigation behaviors in different phases. Supporting implications from prior literature, the hybrid model provided the best fit regardless of navigation requirements, suggesting the majority of participants rely on a blend of model-free (route-following) and model-based (cognitive mapping) learning in such navigation scenarios. Furthermore, consistent with a key prediction, there was a correlation in the hybrid model between the weight on model-based learning (i.e., navigation strategy) and the navigator’s exploration vs. exploitation tendency (i.e., consistency of using such navigation strategy), which was modulated by navigation task requirements. Together, we not only show how computational findings from RL align with the spatial navigation literature, but also reveal how the relationship between navigation strategy and a person’s consistency using such strategies changes as navigation requirements change.
Classifying grains using behaviour-informed machine learning
Authors: Laudari Sudip , Marks Benjy , Rognon Pierre
Published: August 2022

Sorting granular materials such as ores, coffee beans, cereals, gravels and pills is essential for applications in mineral processing, agriculture and waste recycling. Existing sorting methods are based on the detection of contrast in grain properties including size, colour, density and chemical composition. However, many grain properties cannot be directly detected in-situ, which significantly impairs sorting efficacy. We show here that a simple neural network can infer contrast in a wide range of grain properties by detecting patterns in their observable kinematics. These properties include grain size, density, stiffness, friction, dissipation and adhesion. This method of classification based on behaviour can significantly widen the range of granular materials that can be sorted. It can similarly be applied to enhance the sorting of other particulate materials including cells and droplets in microfluidic devices.
Nomograms predicting cancer-specific survival for stage IV colorectal cancer with synchronous lung metastases
Authors: Cheng Pu , Chen Haipeng , Huang Fei , Li Jiyun , Liu Hengchang , Zheng Zhaoxu , Lu Zhao
Published: August 2022

This study aimed to establish a nomogram for the prediction of cancer-specific survival (CSS) of CRC patients with synchronous LM. The final prognostic nomogram based on prognostic factors was evaluated by concordance index (C-index), time-dependent receiver operating characteristic curves, and calibration curves. In the training and validation groups, the C-index for the nomogram was 0.648 and 0.638, and the AUC was 0.793 and 0.785, respectively. The high quality of the calibration curves in the nomogram models for CSS at 1-, 3-, and 5-year was observed. The nomogram model provided a conventional and useful tool to evaluate the 1-, 3-, and 5-year CSS of CRC patients with synchronous LM.
Clinical significance of STING expression and methylation in lung adenocarcinoma based on bioinformatics analysis
Authors: lin Ze , Liu Yu , Lin Peng , Li Jinping , Gan Jinfeng
Published: August 2022

The role of stimulator of interferon genes [STING, also known as transmembrane protein 173 (TMEM173)] in various human cancers has begun to emerge. However, the clinical value of STING in lung adenocarcinoma (LUAD) remains elusive. This study aims to elucidate the clinical significance of STING expression and methylation in LUAD. Here, through analyzing data from public resources, we found that both the mRNA and protein expression of STING were reduced in lung cancer. Moreover, lower expression of STING was associated with a worse prognosis in LUAD, but not lung squamous cell carcinoma (LUSC). Of note, higher methylation of STING was found in LUAD and had the potential to distinguish LUAD tissues from adjacent non-tumor lung tissues and correlated with unfavorable outcomes. Furthermore, the methylation of STING could serve as an independent prognostic indicator for both the overall survival (OS) and disease-free survival (DFS) of LUAD patients. Additionally, the constructed nomogram exhibited a favorable predictive accuracy in predicting the probability of 1- and 2-year OS. Our findings suggest that the mRNA expression, and especially the DNA methylation of STING, have the potential to be prognostic indicators for LUAD patients.
High-frequency stimulation of the subthalamic nucleus induces a sustained inhibition of serotonergic system via loss of cell phenotype
Authors: Alosaimi Faisal , Temel Yasin , Hescham Sarah , Witzig Victoria S. , Almasabi Faris , Tan Sonny K. H. , Jahanshahi Ali
Published: August 2022

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become a standard treatment for Parkinson’s disease (PD). However, in a considerable number of patients debilitating psychiatric side-effects occur. Recent research has revealed that external stimuli can alter the neurotransmitters’ homeostasis in neurons, which is known as “neurotransmitter respecification”. Herein, we addressed if neurotransmitter respecification could be a mechanism by which DBS suppresses the serotonergic function in the dorsal raphe nucleus (DRN) leading to mood changes. We infused transgenic 5-HT-Cre (ePET-Cre) mice with AAV viruses to achieve targeted expression of eYFP and the genetically encoded calcium indicator GCaMP6s in the DRN prior to methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. Mice received bilateral DBS electrodes in the STN and an optic fiber in the DRN for calcium photometry. MPTP-treated mice demonstrated behavioral and histological PD phenotype, whereas all STN-DBS animals exhibited an increased immobility time in the forced swim test, reduced calcium activity, and loss of tryptophan hydroxylase-2 expression in the DRN. Given the prominent role of calcium transients in mediating neurotransmitter respecification, these results suggest a loss of serotonergic phenotype in the DRN following STN-DBS. These findings indicate that loss of serotonergic cell phenotype may underlie the unwanted depressive symptoms following STN-DBS.
Demonstration of a two-bit controlled-NOT quantum-like gate using classical acoustic qubit-analogues
Authors: Runge Keith , Hasan M. Arif , Levine Joshua A. , Deymier Pierre A.
Published: August 2022

The Controlled-NOT (CNOT) gate is the key to unlock the power of quantum computing as it is a fundamental component of a universal set of gates. We demonstrate the operation of a two-bit C-NOT quantum-like gate using classical qubit acoustic analogues, called herein logical phi-bits. The logical phi-bits are supported by an externally driven nonlinear acoustic metamaterial composed of a parallel array of three elastically coupled waveguides. A logical phi-bit has a two-state degree of freedom associated with the two independent relative phases of the acoustic wave in the three waveguides. A simple physical manipulation involving the detuning of the frequency of one of the external drivers is shown to operate on the complex vectors in the Hilbert space of pairs of logical phi-bits. This operation achieves a systematic and predictable C-NOT gate with unambiguously measurable input and output. The possibility of scaling the approach to more phi-bits is promising.
Binary dose level classification of tumour microvascular response to radiotherapy using artificial intelligence analysis of optical coherence tomography images
Authors: Majumdar Anamitra , Allam Nader , Zabel W. Jeffrey , Demidov Valentin , Flueraru Costel , Vitkin I. Alex
Published: August 2022

The dominant consequence of irradiating biological systems is cellular damage, yet microvascular damage begins to assume an increasingly important role as the radiation dose levels increase. This is currently becoming more relevant in radiation medicine with its pivot towards higher-dose-per-fraction/fewer fractions treatment paradigm (e.g., stereotactic body radiotherapy (SBRT)). We have thus developed a 3D preclinical imaging platform based on speckle-variance optical coherence tomography (svOCT) for longitudinal monitoring of tumour microvascular radiation responses in vivo. Here we present an artificial intelligence (AI) approach to analyze the resultant microvascular data. In this initial study, we show that AI can successfully classify SBRT-relevant clinical radiation dose levels at multiple timepoints (t = 2–4 weeks) following irradiation (10 Gy and 30 Gy cohorts) based on induced changes in the detected microvascular networks. Practicality of the obtained results, challenges associated with modest number of animals, their successful mitigation via augmented data approaches, and advantages of using 3D deep learning methodologies, are discussed. Extension of this encouraging initial study to longitudinal AI-based time-series analysis for treatment outcome predictions at finer dose level gradations is envisioned.