bluuebunny/crossref_metadata_2025 huggingface dataset:
Dehydrated thin film media to rapidly estimate bioburden for planetary protection flight implementation
Authors: Dean Zachary S. , Stott Kristina , Schubert Wayne , Seto Emily P. , Chandrapati Sailaja
Published: July 2023

Planetary Protection (PP) is the practice of safeguarding solar system bodies from terrestrial biological contamination and screening the Earth against potentially harmful extraterrestrial biological contamination. On Earth, cleanrooms and spacecraft surfaces are assayed using swabs and wipes that are then heat shocked for 15 min at 80°C to select for spores. The samples are further processed using the pour-plate method and Petri plates (TSA plates), with trypticase soy agar (TSA) serving as the growth medium. This sampling and processing procedure, called the NASA Standard Assay (NSA), is used by PP engineers around the world. Recent years have seen an increase in the incorporation of state-of-the-art technology, such as membrane filtration, into the NSA, with a push for implementing environmentally friendly technology into day-to-day activities. Dehydrated thin film media, such as Petrifilm Rapid Aerobic Count (RAC) plates, suit these goals as an alternative method to TSA plates. RAC plates show bacterial growth (and distinguish colonies from foreign particles such as bubbles) faster than TSA plates due to the incorporation of chromogenic colour indicators in the media. RAC plates also possess a much smaller environmental footprint than TSA plates, and are designed to evaluate even some of the challenging-to-detect environmental organisms, including spreaders that fill over 25% of the plate area in only a few hours. With these benefits in mind the PP Group at the NASA Jet Propulsion Laboratory took on the task of comparing RAC plates directly to TSA plates within the context of the NSA. Not only were the RAC plates able to detect surface environmental samples and in vitro spiked samples equivalent to NSA-processed TSA plates, but spreader organisms were countable on RAC plates at culture densities 10- to 100-fold greater than on TSA plates. In addition, RAC plates showed a robust, linear detection capability when challenged with membrane filter incorporation and organisms were easily acquired from RAC plates for archiving or post-processing experiments including MALDI-TOF bacterial identification. With their ease of use, small footprint, and both rapid and accurate bioburden measurements, RAC plates have the potential to overcome limitations posed by current PP culturing protocols.
Collaborating to reduce food waste: building collaborative advantage in local food systems
Authors: Nadeau Nikki , Koebele Elizabeth A.
Published: July 2023

Food loss and waste throughout the food supply chain is a growing issue with significant economic, social and environmental implications. Wasted food represents lost profits for the food industry, increased food insecurity in communities and the unnecessary production of greenhouse gas emissions, among many other detrimental consequences. Due to the large number of stakeholders involved in the food supply chain and the complexity of their relationships, there is increasing interest in addressing food waste issues through collaborative governance approaches, such as food policy councils (FPCs). Assessing how FPCs engage diverse stakeholders and organizations in food waste reduction efforts can provide important lessons for improving local food systems governance more broadly and contribute to the creation of more sustainable food systems. To do this, we leverage the theoretical concept of ‘collaborative advantage’ to analyze how FPCs foster collaboration, both internally and with external partners, to achieve policy and programmatic goals that individual stakeholders could not achieve alone. Drawing on plan documents and semi-structured interviews with members of five FPCs across the USA, we find that FPCs can foster collaborative advantage by establishing comprehensive food system plans, systematically measuring progress toward objectives, and transparently communicating the evidence of their progress to the communities they serve.
HESIOD'S HOLISTIC AUTHORITY IN NEOPLATONIST EXEGESIS
Authors: Wood Connor Purcell
Published: July 2023

The Neoplatonist scholarch Proclus defined three categories of poetry: inspired, ‘middle’ and mimetic. Traditionally it has been thought that he considered only Homer to have excelled in all three, while other poets could fulfil one or at most two functions. It will be shown that Proclus also conceived of Hesiod as excelling in all three types and thereby assimilated Hesiodic authority to Homeric. He also considered Orpheus but assigned his poetry to just one category, not all three. In doing this, he increased his own authority as a teacher-hierophant, contributing to the dialogue between pagan Platonism and Christianity over the inspiration of texts.
Private Equity Blues: Warner Music Group, Nonesuch Records, and Jazz in the Era of Financialization
Authors: Chapman Dale
Published: July 2023

Since the 1980s, the Nonesuch label, a longstanding subsidiary of the Warner Music Group (WMG), has become noteworthy for its steady market performance during a period of volatility for media multinationals. Nonesuch Records, having once been an adventurous boutique classical label under Teresa Sterne, has developed over the last three decades as a creatively idiosyncratic and commercially successful “adult” imprint under Robert Hurwitz, the erstwhile director of the Munich-based Edition of Contemporary Music jazz label.

Nonesuch has not historically been understood as a jazz label, though it has served as a home for a few jazz acts, including Bill Frisell, Fred Hersch, and the World Saxophone Quartet. By the early years of the new millennium, though, Nonesuch had become one of the few major label subsidiaries willing to maintain an active roster of jazz instrumentalists, harnessing its diversified roster as a source of strength.

This paper examines the Nonesuch label's cultivation of a distinctive jazz niche and situates this development against the backdrop of a period of structural turbulence for the WMG. The leveraged buyout of WMG in 2004, which precipitated the dissolution of the Warner Jazz subsidiary and the transfer of much of its jazz roster to Nonesuch, reflects a contemporary logic of financialization, where value extraction has become the overriding goal of corporate restructuring. Mergers and acquisitions enacted at the uppermost reaches of major label corporate hierarchies pass along significant costs to the label subsidiaries and their artist rosters, installing precarity at the core of the music industry's creative ecologies.
Multi‐Wavelength (L and S Band) Study of Ionospheric Irregularities From an Anomaly Crest Location
Authors: Biswas Trisani , Weiss Jan‐Peter , Paul Ashik
Published: July 2023

This paper reports observation of moderate to intense scintillations, at S band of Indian Regional Navigation Satellite System (IRNSS). During current solar cycle 25, these occurrences are probably being reported for the first time, from a low‐latitude station Calcutta (22.58°N, 88.38°E geographic; magnetic dip 34.54°), located near the northern crest of Equatorial Ionization Anomaly. Efforts have been made to analyze irregularity dynamics at IRNSS S band, along with a comparative study at GNSS L1 to characterize occurrence and evolution of multiscale irregularity structures. Power spectral analysis technique has been applied on recorded C/NO, during scintillation patches, to measure east‐west zonal drift velocity. Efforts are also made to study intensity of signal perturbation at L5 frequency of IRNSS, compared to S band, when observed simultaneously, during period of ionospheric scintillation. Concurrent irregularity dynamics at L1, L5, and S band, particularly from a low‐latitude station, has not been extensively reported earlier. Data is recorded during vernal equinox (February–April 2022) of current solar cycle. Results of this study show occurrence of simultaneous night‐time scintillation at L1, L5, and S band. East‐west zonal drift velocity of irregularity, obtained from S band observations are found to decrease with the progress of time during 20–23 LT having a maximum value of 125 m/s. At GNSS L1, hourly average value of the velocity, is observed to maximize during 20–21 LT. Simultaneous observation of scintillation effects at L5 and S band of IRNSS led to loss‐of‐lock at L5, while no such occurrence was noted at S band.
Variations in the 30–60‐Day Intra‐Seasonal Variability of Spring Precipitation Over the Mid‐Low Reaches of the Yangtze River and the Possible Mechanism
Authors: Yu Shui , Sun Jianqi
Published: July 2023

The precipitation intra‐seasonal variability (ISV) has an important influence on extreme precipitation events, profoundly influencing agricultural activities over the mid‐low reaches of the Yangtze River (MLRYR). Spectrum analysis reveals the existence of 30–60‐day ISV in the MLRYR spring precipitation. The mechanism analysis indicates that, on the intra‐seasonal time scale, the MLRYR precipitation ISV is primarily driven by a wave train over the Eurasian continent. The wave train, with an anomalous anticyclone (cyclone) over the East European Plain and an anomalous cyclone (anticyclone) over Central Asia, could cause more (less) precipitation over the MLRYR. On the inter‐annual and inter‐decadal time scales, the precipitation ISV intensity is influenced by a meridional dipole pattern of the westerly jet stream (WJS) over the Eurasian continent. The positive WJS pattern facilitates the barotropic instability generation and 30–60‐day ISV growth over the East European Plain. Therefore, the ISV intensity of the pronounced wave train is enhanced and further intensifies the MLRYR spring precipitation ISV. In contrast, the negative WJS pattern is unfavorable for regional barotropic instability generation, and therefore the spring precipitation ISV intensity over the MLRYR would be weak. Further analysis shows that the underlying snow cover and soil temperature anomalies could have a contribution to forming the WJS dipole pattern through changing the meridional temperature gradient. The results of this study could deepen our understanding of the spring precipitation ISV over the MLRYR and the mechanisms.
Chemical Weathering Intensity as a Reliable Indicator for Southwest Summer Monsoon Reconstruction: Evidence From Clay Minerals of Qionghai Lake Sediments Since the Last Glacial Maximum
Authors: Yu Xiaoli , Wang Gen , Zhang Ting , Ma Xueyun , Zhang Xiaomei , Li Lun , Li Zelong , Guo Zengguang , Wei Zhifu , Wang Yongli , Zhou Shixin
Published: July 2023

Studying the evolution history of the southwest summer monsoon (SSM) throughout geological time, particularly during its strongest period in the Holocene, can improve our understanding of its variation and driving mechanisms, and even help predict future climate changes, due to its significant social and economic implications. Here, we reconstructed the history of chemical weathering intensity since the Last Glacial Maximum (LGM) based on clay mineral proxies [(illite/smectite)/(illite + chlorite) and illite crystallinity] obtained from Qionghai Lake sediments and examined its response to paleoclimate and SSM. Our findings indicate that the intensity of chemical weathering generally aligned with changes in paleoclimate, exhibiting strong chemical weathering intensity during warm and humid climate conditions. In addition, the intensity of chemical weathering basically tracks the evolution of the SSM since the LGM. Our results support the view that the highest SSM intensity occurred during the early‐middle Holocene, followed by gradual weakening during the late Holocene, with Northern Hemisphere summer insolation being the primary driver of the SSM evolution. The variations of the SSM and the corresponding intensity of chemical weathering were also influenced by the cumulative effects of glacier boundary conditions, North Atlantic climate fluctuations, and Intertropical Convergence Zone migrations.
Lower Crustal Rheology Controls Strain Partitioning and Mode of Intracontinental Deformation
Authors: Xu Xi , Zuza Andrew V. , Yin An , Yu Peng , Chen Zhiyong , Zhao Chongjin , Wang Baodi , Chen Hanlin , Lin Xiubin , Wu Lei , Kuang Xingtao , Tian Hefeng , Yin Qihang , Yang Shufeng
Published: July 2023

The factors that control strain partitioning along plate boundaries and within continental interiors remains poorly resolved. Plate convergence may be accommodated via distributed crustal shortening or discrete crustal‐scale strike‐slip faulting, but what controls these differing modes of deformation is debated. Here we address this question by examining the actively deforming regions that surround the Tarim Basin in central Asia, where deformation is uniquely partitioned into predominately strike‐slip faults in the east and distributed fold‐thrust belts in the west to accommodate Cenozoic India‐Asia plate convergence. We present integrated geological and geophysical observations to elucidate patterns in crustal deformation and compositional structure in and around the Tarim Basin. The thrust‐dominated western Tarim Basin correlates with a strongly‐magnetic lower crust, whereas strike‐slip faulting along the eastern margins of the Tarim Basin lack such magnetic signals. We suggest that the lower crust of the western Tarim is more mafic and stronger than in the east, which impacts intra‐plate strain partitioning. A stronger lower crust results in vertical decoupling to drive mid‐crust horizontal detachments and facilitate thrust faulting, whereas a more homogenized crust favored vertical transcrustal strike‐slip faulting. These rheological differences likely originated from the impingement of the Permian Tarim plume focused in the west. A comparison with the Longmen Shan of eastern Tibetan Plateau reveals remarkably similar strain partitioning that correlates with variations in foreland rheology. Our results highlight how variations in lower‐crust viscosity impact strain partitioning in an intra‐plate setting and how plume processes exert a strong control on later continental tectonic processes.
Metastatic pattern of ovarian cancer delineated by tracing the evolution of mitochondrial DNA mutations
Authors: Xu Zhiyang , Zhou Kaixiang , Wang Zhenni , Liu Yang , Wang Xingguo , Gao Tian , Xie Fanfan , Yuan Qing , Gu Xiwen , Liu Shujuan , Xing Jinliang
Published: July 2023

Ovarian cancer (OC) is the most lethal gynecologic tumor and is characterized by a high rate of metastasis. Challenges in accurately delineating the metastatic pattern have greatly restricted the improvement of treatment in OC patients. An increasing number of studies have leveraged mitochondrial DNA (mtDNA) mutations as efficient lineage-tracing markers of tumor clonality. We applied multiregional sampling and high-depth mtDNA sequencing to determine the metastatic patterns in advanced-stage OC patients. Somatic mtDNA mutations were profiled from a total of 195 primary and 200 metastatic tumor tissue samples from 35 OC patients. Our results revealed remarkable sample-level and patient-level heterogeneity. In addition, distinct mtDNA mutational patterns were observed between primary and metastatic OC tissues. Further analysis identified the different mutational spectra between shared and private mutations among primary and metastatic OC tissues. Analysis of the clonality index calculated based on mtDNA mutations supported a monoclonal tumor origin in 14 of 16 patients with bilateral ovarian cancers. Notably, mtDNA-based spatial phylogenetic analysis revealed distinct patterns of OC metastasis, in which a linear metastatic pattern exhibited a low degree of mtDNA mutation heterogeneity and a short evolutionary distance, whereas a parallel metastatic pattern showed the opposite trend. Moreover, a mtDNA-based tumor evolutionary score (MTEs) related to different metastatic patterns was defined. Our data showed that patients with different MTESs responded differently to combined debulking surgery and chemotherapy. Finally, we observed that tumor-derived mtDNA mutations were more likely to be detected in ascitic fluid than in plasma samples. Our study presents an explicit view of the OC metastatic pattern, which sheds light on efficient treatment for OC patients.
Cancer-associated fibroblasts: from basic science to anticancer therapy
Authors: Yang Dakai , Liu Jing , Qian Hui , Zhuang Qin
Published: July 2023

Cancer-associated fibroblasts (CAFs), as a central component of the tumor microenvironment in primary and metastatic tumors, profoundly influence the behavior of cancer cells and are involved in cancer progression through extensive interactions with cancer cells and other stromal cells. Furthermore, the innate versatility and plasticity of CAFs allow their education by cancer cells, resulting in dynamic alterations in stromal fibroblast populations in a context-dependent manner, which highlights the importance of precise assessment of CAF phenotypical and functional heterogeneity. In this review, we summarize the proposed origins and heterogeneity of CAFs as well as the molecular mechanisms regulating the diversity of CAF subpopulations. We also discuss current strategies to selectively target tumor-promoting CAFs, providing insights and perspectives for future research and clinical studies involving stromal targeting.
Mesenchymal stromal cells facilitate resolution of pulmonary fibrosis by miR-29c and miR-129 intercellular transfer
Authors: Nataliya Basalova , Mikhail Arbatskiy , Vladimir Popov , Olga Grigorieva , Maksim Vigovskiy , Ivan Zaytsev , Ekaterina Novoseletskaya , Georgy Sagaradze , Natalia Danilova , Pavel Malkov , Andrey Cherniaev , Maria Samsonova , Maxim Karagyaur , Anastasiya Tolstoluzhinskaya , Uliana Dyachkova , Zhanna Akopyan , Vsevolod Tkachuk , Natalia Kalinina , Anastasiya Efimenko
Published: July 2023

To date, pulmonary fibrosis remains an unmet medical need. In this study, we evaluated the potency of mesenchymal stromal cell (MSC) secretome components to prevent pulmonary fibrosis development and facilitate fibrosis resolution. Surprisingly, the intratracheal application of extracellular vesicles (MSC-EVs) or the vesicle-depleted secretome fraction (MSC-SF) was not able to prevent lung fibrosis when applied immediately after the injury caused by bleomycin instillation in mice. However, MSC-EV administration induced the resolution of established pulmonary fibrosis, whereas the vesicle-depleted fraction did not. The application of MSC-EVs caused a decrease in the numbers of myofibroblasts and FAPa+ progenitors without affecting their apoptosis. Such a decrease likely occurred due to their dedifferentiation caused by microRNA (miR) transfer by MSC-EVs. Using a murine model of bleomycin-induced pulmonary fibrosis, we confirmed the contribution of specific miRs (miR-29c and miR-129) to the antifibrotic effect of MSC-EVs. Our study provides novel insights into possible antifibrotic therapy based on the use of the vesicle-enriched fraction of the MSC secretome.
TXNIP: A key protein in the cellular stress response pathway and a potential therapeutic target
Authors: Choi Eui-Hwan , Park Sun-Ji
Published: July 2023

Thioredoxin-interacting protein (TXNIP), which is also known as thioredoxin-binding protein 2 (TBP2), directly interacts with the major antioxidant protein thioredoxin (TRX) and inhibits its antioxidant function and expression. However, recent studies have demonstrated that TXNIP is a multifunctional protein with functions beyond increasing intracellular oxidative stress. TXNIP activates endoplasmic reticulum (ER) stress-mediated nucleotide-binding oligomerization domain (NOD)-like receptor protein-3 (NLRP3) inflammasome complex formation, triggers mitochondrial stress-induced apoptosis, and stimulates inflammatory cell death (pyroptosis). These newly discovered functions of TXNIP highlight its role in disease development, especially in response to several cellular stress factors. In this review, we provide an overview of the multiple functions of TXNIP in pathological conditions and summarize its involvement in various diseases, such as diabetes, chronic kidney disease, and neurodegenerative diseases. We also discuss the potential of TXNIP as a therapeutic target and TXNIP inhibitors as novel therapeutic drugs for treating these diseases.
Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential
Authors: Xu Xuemeng , Peng Qiu , Jiang Xianjie , Tan Shiming , Yang Yiqing , Yang Wenjuan , Han Yaqian , Chen Yuyu , Oyang Linda , Lin Jinguan , Xia Longzheng , Peng Mingjing , Wu Nayiyuan , Tang Yanyan , Li Jinyun , Liao Qianjin , Zhou Yujuan
Published: July 2023

Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cancer cells, metabolic pathway activity varies during tumorigenesis and cancer progression, indicating regulated metabolic plasticity. Metabolic changes are often closely related to epigenetic changes, such as alterations in the expression or activity of epigenetically modified enzymes, which may exert a direct or an indirect influence on cellular metabolism. Therefore, exploring the mechanisms underlying epigenetic modifications regulating the reprogramming of tumor cell metabolism is important for further understanding tumor pathogenesis. Here, we mainly focus on the latest studies on epigenetic modifications related to cancer cell metabolism regulations, including changes in glucose, lipid and amino acid metabolism in the cancer context, and then emphasize the mechanisms related to tumor cell epigenetic modifications. Specifically, we discuss the role played by DNA methylation, chromatin remodeling, noncoding RNAs and histone lactylation in tumor growth and progression. Finally, we summarize the prospects of potential cancer therapeutic strategies based on metabolic reprogramming and epigenetic changes in tumor cells.
Immune regulation through tryptophan metabolism
Authors: Seo Su-Kil , Kwon Byungsuk
Published: July 2023

Amino acids are fundamental units of molecular components that are essential for sustaining life; however, their metabolism is closely interconnected to the control systems of cell function. Tryptophan (Trp) is an essential amino acid catabolized by complex metabolic pathways. Several of the resulting Trp metabolites are bioactive and play central roles in physiology and pathophysiology. Additionally, various physiological functions of Trp metabolites are mutually regulated by the gut microbiota and intestine to coordinately maintain intestinal homeostasis and symbiosis under steady state conditions and during the immune response to pathogens and xenotoxins. Cancer and inflammatory diseases are associated with dysbiosis- and host-related aberrant Trp metabolism and inactivation of the aryl hydrocarbon receptor (AHR), which is a receptor of several Trp metabolites. In this review, we focus on the mechanisms through which Trp metabolism converges to AHR activation for the modulation of immune function and restoration of tissue homeostasis and how these processes can be targeted using therapeutic approaches for cancer and inflammatory and autoimmune diseases.
Genomic characteristics of triple negative apocrine carcinoma: a comparison to triple negative breast cancer
Authors: Kim Ji-Yeon , Park Sabin , Cho Eun Yoon , Lee Jeong Eon , Jung Hae Hyun , Chae Byung Joo , Kim Seok Won , Nam Seok Jin , Cho Soo Youn , Park Yeon Hee , Ahn Jin Seok , Lee Semin , Im Young-Hyuck
Published: July 2023

Apocrine carcinoma is a rare breast cancer subtype. As such, the genomic characteristics of apocrine carcinoma with triple negative immunohistochemical results (TNAC), which has been treated as triple negative breast cancer (TNBC), have not been revealed. In this study, we evaluated the genomic characteristics of TNAC compared to TNBC with low Ki-67 (LK-TNBC). In the genetic analysis of 73 TNACs and 32 LK-TNBCs, the most frequently mutated driver gene in TNAC was TP53 (16/56, 28.6%), followed by PIK3CA (9/56, 16.1%), ZNF717 (8/56, 14.3%), and PIK3R1 (6/56, 10.71%). Mutational signature analysis showed enrichment of defective DNA mismatch repair (MMR)-related signatures (SBS6 and SBS21) and the SBS5 signature in TNAC, whereas an APOBEC activity-associated mutational signature (SBS13) was more prominent in LK-TNBC (Student’s t test, p < 0.05). In intrinsic subtyping, 38.4% of TNACs were classified as luminal A, 27.4% as luminal B, 26.0% as HER2-enriched (HER2-E), 2.7% as basal, and 5.5% as normal-like. The basal subtype was the most dominant subtype (43.8%) in LK-TNBC (p < 0.001), followed by luminal B (21.9%), HER2-E (21.9%), and luminal A (12.5%). In the survival analysis, TNAC had a five-year disease-free survival (DFS) rate of 92.2% compared to 59.1% for LK-TNBC (P = 0.001) and a five-year overall survival (OS) rate of 95.3% compared to 74.6% for LK-TNBC (P = 0.0099). TNAC has different genetic characteristics and better survival outcomes than LK-TNBC. In particular, normal-like and luminal A subtypes in TNAC have much better DFS and OS than other intrinsic subtypes. Our findings are expected to impact medical practice for patients diagnosed with TNAC.
Transcriptional regulation of Glis2 in hepatic fibrosis
Authors: Gong Huan-Yu , Zhou Peng-Cheng , Zhang Hao-Ye , Chen Li-Min , Zhou Yang-Mei , Liu Zhen-Guo
Published: July 2023

The role of Gli-similar 2 (Glis2) in hepatic fibrosis (HF) is controversial. In this study, we focused on the functional and molecular mechanisms involved in the Glis2-mediated activation of hepatic stellate cells (HSCs)—a milestone event leading to HF. The expression levels of Glis2 mRNA and protein were significantly decreased in the liver tissues of patients with severe HF and in mouse fibrotic liver tissues as well as HSCs activated by TGFβ1. Functional studies indicated that upregulated Glis2 significantly inhibited HSC activation and alleviated BDL-induced HF in mice. Downregulation of Glis2 was found to correlate significantly with DNA methylation of the Glis2 promoter mediated by methyltransferase 1 (DNMT1), which restricted the binding of hepatic nuclear factor 1-α (HNF1-α), a liver-specific transcription factor, to Glis2 promoters. In addition, the enrichment of DNMT1 in the Glis2 promoter region was mediated by metastasis-associated lung adenocarcinoma transcriptor-1 (MALAT1) lncRNA, leading to transcriptional silencing of Glis2 and activation of HSCs. In conclusion, our findings reveal that the upregulation of Glis2 can maintain the resting state of HSCs. The decreased expression of Glis2 under pathological conditions may lead to the occurrence and development of HF with the expression silencing of DNA methylation mediated by MALAT1 and DNMT1.
ROR1-STAT3 signaling contributes to ovarian cancer intra-tumor heterogeneity
Authors: Piki Emilia , Dini Alice , Raivola Juuli , Salokas Kari , Zhang Kaiyang , Varjosalo Markku , Pellinen Teijo , Välimäki Katja , Veskimäe Kristina Tabor , Staff Synnöve , Hautaniemi Sampsa , Murumägi Astrid , Ungureanu Daniela
Published: July 2023

Wnt pathway dysregulation through genetic and non-genetic alterations occurs in multiple cancers, including ovarian cancer (OC). The aberrant expression of the non-canonical Wnt signaling receptor ROR1 is thought to contribute to OC progression and drug resistance. However, the key molecular events mediated by ROR1 that are involved in OC tumorigenesis are not fully understood. Here, we show that ROR1 expression is enhanced by neoadjuvant chemotherapy, and Wnt5a binding to ROR1 can induce oncogenic signaling via AKT/ERK/STAT3 activation in OC cells. Proteomics analysis of isogenic ROR1-knockdown OC cells identified STAT3 as a downstream effector of ROR1 signaling. Transcriptomics analysis of clinical samples (n = 125) revealed that ROR1 and STAT3 are expressed at higher levels in stromal cells than in epithelial cancer cells of OC tumors, and these findings were corroborated by multiplex immunohistochemistry (mIHC) analysis of an independent OC cohort (n = 11). Our results show that ROR1 and its downstream STAT3 are co-expressed in epithelial as well as stromal cells of OC tumors, including cancer-associated fibroblasts or CAFs. Our data provides the framework to expand the clinical utility of ROR1 as a therapeutic target to overcome OC progression.
A biological camera that captures and stores images directly into DNA
Authors: Lim Cheng Kai , Yeoh Jing Wui , Kunartama Aurelius Andrew , Yew Wen Shan , Poh Chueh Loo
Published: July 2023

The increasing integration between biological and digital interfaces has led to heightened interest in utilizing biological materials to store digital data, with the most promising one involving the storage of data within defined sequences of DNA that are created by de novo DNA synthesis. However, there is a lack of methods that can obviate the need for de novo DNA synthesis, which tends to be costly and inefficient. Here, in this work, we detail a method of capturing 2-dimensional light patterns into DNA, by utilizing optogenetic circuits to record light exposure into DNA, encoding spatial locations with barcoding, and retrieving stored images via high-throughput next-generation sequencing. We demonstrate the encoding of multiple images into DNA, totaling 1152 bits, selective image retrieval, as well as robustness to drying, heat and UV. We also demonstrate successful multiplexing using multiple wavelengths of light, capturing 2 different images simultaneously using red and blue light. This work thus establishes a ‘living digital camera’, paving the way towards integrating biological systems with digital devices.
Spatiotemporal proteomic atlas of multiple brain regions across early fetal to neonatal stages in cynomolgus monkey
Authors: Wei Jingkuan , Dai Shaoxing , Yan Yaping , Li Shulin , Yang Pengpeng , Zhu Ran , Huang Tianzhuang , Li Xi , Duan Yanchao , Wang Zhengbo , Ji Weizhi , Si Wei
Published: July 2023

Fetal stages are critical periods for brain development. However, the protein molecular signature and dynamics of the human brain remain unclear due to sampling difficulty and ethical limitations. Non-human primates present similar developmental and neuropathological features to humans. This study constructed a spatiotemporal proteomic atlas of cynomolgus macaque brain development from early fetal to neonatal stages. Here we showed that (1) the variability across stages was greater than that among brain regions, and comparisons of cerebellum vs. cerebrum and cortical vs. subcortical regions revealed region-specific dynamics across early fetal to neonatal stages; (2) fluctuations in abundance of proteins associated with neural disease suggest the risk of nervous disorder at early fetal stages; (3) cross-species analysis (human, monkey, and mouse) and comparison between proteomic and transcriptomic data reveal the proteomic specificity and genes with mRNA/protein discrepancy. This study provides insight into fetal brain development in primates.
Rapid strengthening of westerlies accompanied intensification of Northern Hemisphere glaciation
Authors: Bridges Joshua D. , Tarduno John A. , Cottrell Rory D. , Herbert Timothy D.
Published: July 2023

The trigger, pace, and nature of the intensification of Northern Hemisphere Glaciation (iNHG) are uncertain, but can be probed by study of ODP Site 1208 North Pacific marine sediments. Herein, we present magnetic proxy data that indicate a 4-fold increase of dust between ~ 2.73 and ~ 2.72 Ma, with subsequent increases at the start of glacials thereafter, indicating a strengthening of the mid-latitude westerlies. Moreover, a permanent shift in dust composition after 2.72 Ma is observed, consistent with drier conditions in the source region and/or the incorporation of material which could not have been transported via the weaker Pliocene winds. The sudden increase in our dust proxy data, a coeval rapid rise in dust recorded by proxy dust data in the North Atlantic (Site U1313), and the Site 1208 shift in dust composition, suggest that the iNHG represents a permanent crossing of a climate threshold toward global cooling and ice sheet growth, ultimately driven by lower atmospheric CO2.
Evidence for compositionally distinct upper mantle plumelets since the early history of the Tristan-Gough hotspot
Authors: Homrighausen Stephan , Hoernle Kaj , Hauff Folkmar , Hoyer Patrick A. , Haase Karsten M. , Geissler Wolfram H. , Geldmacher Jörg
Published: July 2023

Recent studies indicate that mantle plumes, which transfer material and heat from the earth’s interior to its surface, represent multifaceted upwellings. The Tristan-Gough hotspot track (South Atlantic), which formed above a mantle plume, documents spatial geochemical zonation in two distinct sub-tracks since ~70 Ma. The origin and the sudden appearance of two distinct geochemical flavors is enigmatic, but could provide insights into the structural evolution of mantle plumes. Sr–Nd–Pb–Hf isotope data from the Late Cretaceous Rio Grande Rise and adjacent Jean Charcot Seamount Chain (South American Plate), which represent the counterpart of the older Tristan-Gough volcanic track (African Plate), extends the bilateral-zonation to ~100 Ma. Our results support recent numerical models, demonstrating that mantle plumes can split into distinct upper mantle conduits, and provide evidence that these plumelets formed at the plume head-to-plume tail transition. We attribute the plume zonation to sampling the geochemically-graded margin of the African Large Low-Shear-Velocity Province.
Dynamic control of hybrid grafted perfect vector vortex beams
Authors: Ahmed Hammad , Ansari Muhammad Afnan , Li Yan , Zentgraf Thomas , Mehmood Muhammad Qasim , Chen Xianzhong
Published: July 2023

Perfect vector vortex beams (PVVBs) have attracted considerable interest due to their peculiar optical features. PVVBs are typically generated through the superposition of perfect vortex beams, which suffer from the limited number of topological charges (TCs). Furthermore, dynamic control of PVVBs is desirable and has not been reported. We propose and experimentally demonstrate hybrid grafted perfect vector vortex beams (GPVVBs) and their dynamic control. Hybrid GPVVBs are generated through the superposition of grafted perfect vortex beams with a multifunctional metasurface. The generated hybrid GPVVBs possess spatially variant rates of polarization change due to the involvement of more TCs. Each hybrid GPVVB includes different GPVVBs in the same beam, adding more design flexibility. Moreover, these beams are dynamically controlled with a rotating half waveplate. The generated dynamic GPVVBs may find applications in the fields where dynamic control is in high demand, including optical encryption, dense data communication, and multiple particle manipulation.
Built structures influence patterns of energy demand and CO2 emissions across countries
Authors: Haberl Helmut , Löw Markus , Perez-Laborda Alejandro , Matej Sarah , Plank Barbara , Wiedenhofer Dominik , Creutzig Felix , Erb Karl-Heinz , Duro Juan Antonio
Published: July 2023

Built structures, i.e. the patterns of settlements and transport infrastructures, are known to influence per-capita energy demand and CO2emissions at the urban level. At the national level, the role of built structures is seldom considered due to poor data availability. Instead, other potential determinants of energy demand and CO2emissions, primarily GDP, are more frequently assessed. We present a set of national-level indicators to characterize patterns of built structures. We quantify these indicators for 113 countries and statistically analyze the results along with final energy use and territorial CO2emissions, as well as factors commonly included in national-level analyses of determinants of energy use and emissions. We find that these indicators are about equally important for predicting energy demand and CO2emissions as GDP and other conventional factors. The area of built-up land per capita is the most important predictor, second only to the effect of GDP.
Neoantigen-specific stem cell memory-like CD4+ T cells mediate CD8+ T cell-dependent immunotherapy of MHC class II-negative solid tumors
Authors: Brightman Spencer E. , Becker Angelica , Thota Rukman R. , Naradikian Martin S. , Chihab Leila , Zavala Karla Soria , Ramamoorthy Premlal Ashmitaa Logandha , Griswold Ryan Q. , Dolina Joseph S. , Cohen Ezra E. W. , Miller Aaron M. , Peters Bjoern , Schoenberger Stephen P.
Published: July 2023

CD4+T cells play key roles in a range of immune responses, either as direct effectors or through accessory cells, including CD8+T lymphocytes. In cancer, neoantigen (NeoAg)-specific CD8+T cells capable of direct tumor recognition have been extensively studied, whereas the role of NeoAg-specific CD4+T cells is less well understood. We have characterized the murine CD4+T cell response against a validated NeoAg (CLTCH129>Q) expressed by the MHC-II-deficient squamous cell carcinoma tumor model (SCC VII) at the level of single T cell receptor (TCR) clonotypes and in the setting of adoptive immunotherapy. We find that the natural CLTCH129>Q-specific repertoire is diverse and contains TCRs with distinct avidities as measured by tetramer-binding assays and CD4 dependence. Despite these differences, CD4+T cells expressing high or moderate avidity TCRs undergo comparable in vivo proliferation to cross-presented antigen from growing tumors and drive similar levels of therapeutic immunity that is dependent on CD8+T cells and CD40L signaling. Adoptive cellular therapy (ACT) with NeoAg-specific CD4+T cells is most effective when TCR-engineered cells are differentiated ex vivo with IL-7 and IL-15 rather than IL-2 and this was associated with both increased expansion as well as the acquisition and stable maintenance of a T stem cell memory (TSCM)-like phenotype in tumor-draining lymph nodes (tdLNs). ACT with TSCM-like CD4+T cells results in lower PD-1 expression by CD8+T cells in the tumor microenvironment and an increased frequency of PD-1+CD8+T cells in tdLNs. These findings illuminate the role of NeoAg-specific CD4+T cells in mediating antitumor immunity via providing help to CD8+T cells and highlight their therapeutic potential in ACT.
Polyhydroxy butyrate biosynthesis by Azotobacter chroococcum MTCC 3858 through groundnut shell as lignocellulosic feedstock using resource surface methodology
Authors: Nagajothi Kasilingam , Murugesan A. G.
Published: July 2023

This work appraises the prospect of utilising groundnut shell hydrolysate as a feedstock used for PHB biosynthesis by Azotobacter chroococcum MTCC 3853 under SMF conditions. Sugar reduction: untreated and pretreated 20% H2SO4 (39.46 g/l and 62.96 g/l, respectively), untreated and enzymatic hydrolysis (142.35 mg/g and 568.94 mg/g). The RSM-CCD optimization method was used to generate augment PHB biosynthesis from groundnut shell hydrolysate (30 g/l), ammonium sulphate (1.5 g/l), ammonium chloride (1.5 g/l), peptone (1.5 g/l), pH 7, 30 °C, and a 48 h incubation time. The most convincing factors (p < 0.0001), coefficient R2 values of biomass 0.9110 and PHB yield 0.9261, PHB production, highest biomass (17.23 g/l), PHB Yield(11.46 g/l), and 66.51 (wt% DCW) values were recorded. The control (untreated GN) PHB yield value of 2.86 g/l increased up to fourfold in pretreated GN. TGA results in a melting range in the peak perceived at 270.55 °C and a DSC peak range of 172.17 °C, correspondingly. According to the results, it furnishes an efficient agricultural waste executive approach by diminishing the production expenditure. It reinforces the production of PHB, thereby shrinking our reliance on fossil fuel-based plastics.
Creating musical features using multi-faceted, multi-task encoders based on transformers
Authors: Greer Timothy , Shi Xuan , Ma Benjamin , Narayanan Shrikanth
Published: July 2023

Computational machine intelligence approaches have enabled a variety of music-centric technologies in support of creating, sharing and interacting with music content. A strong performance on specific downstream application tasks, such as music genre detection and music emotion recognition, is paramount to ensuring broad capabilities for computational music understanding and Music Information Retrieval. Traditional approaches have relied on supervised learning to train models to support these music-related tasks. However, such approaches require copious annotated data and still may only provide insight into one view of music—namely, that related to thespecifictask at hand. We present a new model for generating audio-musical features that support music understanding, leveraging self-supervision and cross-domain learning. After pre-training using masked reconstruction of musical input features using self-attention bidirectional transformers, output representations are fine-tuned using several downstream music understanding tasks. Results show that the features generated by our multi-faceted, multi-task, music transformer model, which we call M3BERT, tend to outperform other audio and music embeddings on several diverse music-related tasks, indicating the potential of self-supervised and semi-supervised learning approaches toward a more generalized and robust computational approach to modeling music. Our work can offer a starting point for many music-related modeling tasks, with potential applications in learning deep representations and enabling robust technology applications.
Lytic Escherichia phage OSYSP acts additively and synergistically with gaseous ozone against Escherichia coli O157:H7 on spinach leaves
Authors: Yesil Mustafa , Kasler David R. , Huang En , Yousef Ahmed E.
Published: July 2023

Bacteriophage and gaseous ozone are evolving as meritorious alternatives to conventional sanitizers in food postharvest applications. Here, we investigated the efficacy of sequential treatments of a lytic bacteriophage and gaseous ozone, during vacuum cooling of fresh produce, against Escherichia coli O157:H7. Spinach leaves were spot-inoculated with 105–107 CFU g−1 E. coli O157:H7 B6-914 and treated with Escherichia phage OSYSP spray (109 PFU g−1), gaseous ozone, or their combination. Vacuum cooling, which preceded or followed phage application but ran concomitantly with ozone treatment, was performed in a custom-made vessel at the following process sequence: vacuum to 28.5 in. Hg, vessel pressurization to 10 psig with gas containing 1.5 g ozone/kg gas-mix, holding for 30 min, and vessel depressurization to ambient pressure. Bacteriophage or gaseous ozone inactivated E. coli O157:H7, applied at different initial populations on spinach leaves, by 1.7–2.0 or 1.8–3.5 log CFU g−1, respectively. At the high inoculum levels tested (7.1 log CFU g−1), sequential treatments of phage and ozone reduced E. coli O157:H7 population by 4.0 log CFU g−1, but when treatment order was reversed (i.e., ozone followed by bacteriophage), the combination synergistically decreased pathogen’s population on spinach leaves by 5.2 log CFU g−1. Regardless the antibacterial application order, E. coli O157:H7 populations, applied initially at ~ 105 CFU g−1, were reduced below the enumeration method’s detection level (i.e., < 101 CFU g−1). The study proved that bacteriophage–ozone combination, applied in conjunction with vacuum cooling, is a potent pathogen intervention strategy in fresh produce post-harvest applications.
Towards risk-targeted seismic hazard models for Europe
Authors: Monti Giorgio , Demartino Cristoforo , Gardoni Paolo
Published: July 2023

Standards and Codes of Practice for designing new constructions and for assessing and strengthening existing ones are usually based on uniform hazard maps, where different Limit States (LSs) are associated with different hazard-exceedance probabilities. This approach yields non-homogeneous LS-exceedance probabilities across a territory, thus failing to achieve the goal of uniform risk throughout a territory. Such lack of uniformity stems from estimating the probability of failure using capacity and demand models. If the capacity of new constructions—or the capacity increase of strengthened existing constructions—are designed based on a prescribed hazard-exceedance probability, then the seismic risk depends on both the structure (depending on the design philosophy and corresponding design objectives), through the capacity model, and the location, through the hazard model. The aim of this study is threefold. First, it provides a seismic probability assessment formulation and a risk-targeted intensity measure based on a linear model in log–log coordinates of the hazard, under the assumption of log-normal capacity and demand. The proposed framework introduces a factor that multiplies the code hazard-based demand to account either for intentional (from design) over-capacity or for undesired (e.g., in existing constructions) under-capacity. Second, this paper shows an application to peak ground accelerations in Europe considering parameters taken from Standards and Codes of Practice. The developed framework is used to determine the risk-target levels of peak ground acceleration used for design in Europe, for both new and existing constructions. Third, the obtained target risk levels are used to determine a risk-based intensity modification factor and a risk-based mean return period modification factor, which can be readily implemented in current Standards to achieve risk-targeted design actions, with equal LS-exceedance probability across the territory. The framework is independent of the chosen hazard-based intensity measure, be it the commonly used peak ground acceleration or any other measure. The results highlight that in large areas of Europe the design peak ground acceleration should be increased to achieve the proposed seismic risk target and that this is particularly significant for existing constructions, given their larger uncertainties and typical low capacity with respect to the code hazard-based demand.
PBRM1 mutations might render a subtype of biliary tract cancers sensitive to drugs targeting the DNA damage repair system
Authors: Zimmer Kai , Kocher Florian , Untergasser Gerold , Kircher Brigitte , Amann Arno , Baca Yasmine , Xiu Joanne , Korn W. Micheal , Berger Martin D. , Lenz Heinz-Josef , Puccini Alberto , Fontana Elisa , Shields Anthony F. , Marshall John L. , Hall Michael , El-Deiry Wafik S. , Hsiehchen David , Macarulla Teresa , Tabernero Josep , Pichler Renate , Khushman Moh’d , Manne Upender , Lou Emil , Wolf Dominik , Sokolova Viktorija , Schnaiter Simon , Zeimet Alain G. , Gulhati Pat , Widmann Gerlig , Seeber Andreas
Published: July 2023

Polybromo-1 (PBRM1) loss of function mutations are present in a fraction of biliary tract cancers (BTCs). PBRM1, a subunit of the PBAF chromatin-remodeling complex, is involved in DNA damage repair. Herein, we aimed to decipher the molecular landscape of PBRM1 mutated (mut) BTCs and to define potential translational aspects. Totally, 1848 BTC samples were analyzed using next-generation DNA-sequencing and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). siRNA-mediated knockdown of PBRM1 was performed in the BTC cell line EGI1 to assess the therapeutic vulnerabilities of ATR and PARP inhibitors in vitro. PBRM1 mutations were identified in 8.1% (n = 150) of BTCs and were more prevalent in intrahepatic BTCs (9.9%) compared to gallbladder cancers (6.0%) or extrahepatic BTCs (4.5%). Higher rates of co-mutations in chromatin-remodeling genes (e.g., ARID1A 31% vs. 16%) and DNA damage repair genes (e.g., ATRX 4.4% vs. 0.3%) were detected in PBRM1-mutated (mut) vs. PBRM1-wildtype (wt) BTCs. No difference in real-world overall survival was observed between PBRM1-mut and PBRM1-wt patients (HR 1.043, 95% CI 0.821–1.325, p = 0.731). In vitro, experiments suggested that PARP ± ATR inhibitors induce synthetic lethality in the PBRM1 knockdown BTC model. Our findings served as the scientific rationale for PARP inhibition in a heavily pretreated PBRM1-mut BTC patient, which induced disease control. This study represents the largest and most extensive molecular profiling study of PBRM1-mut BTCs, which in vitro sensitizes to DNA damage repair inhibiting compounds. Our findings might serve as a rationale for future testing of PARP/ATR inhibitors in PBRM1-mut BTCs.