bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lateglacial Shifts in Seasonality Reconcile Conflicting North Atlantic Temperature Signals
Authors: Bromley Gordon , Putnam Aaron , Hall Brenda , Rademaker Kurt , Thomas Holly , Balter‐Kennedy Allie , Barker Stephen , Rice Donald 
Published: January 2023

AbstractThe accelerating flux of glacial meltwater to the oceans due to global warming is a potential trigger for future climate disturbance. Past disruption of Atlantic Ocean circulation, driven by melting of land‐based ice, is linked in models to reduced ocean‐atmosphere heat transfer and abrupt cooling during stadial events. The most recent stadial, the Younger Dryas (YD), is traditionally viewed as a severe cooling centered on the North Atlantic but with hemispheric influence. However, indications of summer warmth question whether YD cooling was truly year‐round or restricted to winter. Here, we present a beryllium‐10‐dated glacier record from the north‐east North Atlantic, coupled with 2‐D glacier‐climate modeling, to reconstruct Lateglacial summer air temperature patterns. Our record reveals that, contrary to the prevailing model, the last glacial advance in Scotland did not occur during the YD but predated the stadial, while the YD itself was characterized by warming‐driven deglaciation. We argue that these apparently paradoxical findings can be reconciled with regional and global climate events by invoking enhanced North Atlantic seasonality—with anomalously cold winters but warming summers—as an intrinsic response to globally increased poleward heat fluxes.
Hydrothermal growth of KTiOPO4 crystal for electro-optical application
Authors: Zhou Haitao , He Xiaoling , Wu Wenyuan , Tong Jingfang , Wang Jinliang , Zuo Yanbin , Wu Yicheng , Zhang Changlong , Hu Zhanggui 
Published: January 2023

Abstract“New” electro-optical (EO) crystals are hard to find, “old” EO crystals are scarce and each has its own problems, and the demand for high-performance EO crystals by higher power, higher repetition rate, and narrower pulse width laser is realistic and urgent. The EO performance of KTP was recognized as soon as it was discovered, but after more than 40 years of development, the reports, and products of EO devices based on KTP are less than those of other EO crystals, even though KTP is now almost the cheapest nonlinear optical crystal material. In this paper, based on our understanding of the crystal structure of predecessors and ourselves, especially the understanding and practice of quasi-one-dimensional ionic conduction mechanism, we think that crystal growth is the most important reason that affects the controllability of crystal performance. Through a series of science and technology, we realize the growth of large-size crystals with high-optical uniformity, then reduce the absorption of KTP to a very low level, and grow crystals with resistance to electric damage and laser damage. On this basis, reducing the conductivity and improving the uniformity of optical, electrical, piezoelectric, and ferroelectric properties are emphasized. The extinction ratio, piezoelectric ringing effect, and thermal influence of the EO switch based on KTP crystal are tested, and some publicly available progress of using KTP EO devices in high-repetition rate laser is listed. Finally, we are looking forward to the development of KTP EO crystal for the laser system to EO generator for integrated optics.
FRMD3 inhibits the growth and metastasis of breast cancer through the ubiquitination-mediated degradation of vimentin and subsequent impairment of focal adhesion
Authors: Shao Wenjun , Li Jiawei , Piao Qianling , Yao Xinlei , Li Mingyue , Wang Shuyue , Song Zhenbo , Sun Ying , Zheng Lihua , Wang Guannan , Liu Lei , Yu Chunlei , Huang Yanxin , Bao Yongli , Sun Luguo 
Published: January 2023

AbstractRecurrence and metastasis are the main causes of breast cancer (BRCA)-related death and remain a challenge for treatment. In-depth research on the molecular mechanisms underlying BRCA progression has been an important basis for developing precise biomarkers and therapy targets for early prediction and treatment of progressed BRCA. Herein, we identified FERM domain-containing protein 3 (FRMD3) as a novel potent BRCA tumor suppressor which is significantly downregulated in BRCA clinical tissue and cell lines, and low FRMD3 expression has been closely associated with progressive BRCA and shortened survival time in BRCA patients. Overexpression and knockdown experiments have revealed that FRMD3 significantly inhibits BRCA cell proliferation, migration, and invasion in vitro and suppresses BRCA xenograft growth and metastasis in vivo as well. Mechanistically, FRMD3 can interact with vimentin and ubiquitin protein ligase E3A(UBE3A) to induce the polyubiquitin-mediated proteasomal degradation of vimentin, which subsequently downregulates focal adhesion complex proteins and pro-cancerous signaling activation, thereby resulting in cytoskeletal rearrangement and defects in cell morphology and focal adhesion. Further evidence has confirmed that FRMD3-mediated vimentin degradation accounts for the anti-proliferation and anti-metastasis effects of FRMD3 on BRCA. Moreover, the N-terminal ubiquitin-like domain of FRMD3 has been identified as responsible for FRMD3-vimentin interaction through binding the head domain of vimentin and the truncated FRMD3 with the deletion of ubiquitin-like domain almost completely loses the anti-BRCA effects. Taken together, our study indicates significant potential for the use of FRMD3 as a novel prognosis biomarker and a therapeutic target of BRCA and provides an additional mechanism underlying the degradation of vimentin and BRCA progression.
Pericentromeric satellite lncRNAs are induced in cancer-associated fibroblasts and regulate their functions in lung tumorigenesis
Authors: Enukashvily Natella I. , Ponomartsev Nikita V. , Ketkar Avanee , Suezov Roman , Chubar Anna V. , Prjibelski Andrey D. , Shafranskaya Daria D. , Elmshäuser Sabrina , Keber Corinna U. , Stefanova Vera N. , Akopov Andrey L. , Klingmüller Ursula , Pfefferle Petra I. , Stiewe Thorsten , Lauth Matthias , Brichkina Anna I. 
Published: January 2023

AbstractThe abnormal tumor microenvironment (TME) often dictates the therapeutic response of cancer to chemo- and immuno-therapy. Aberrant expression of pericentromeric satellite repeats has been reported for epithelial cancers, including lung cancer. However, the transcription of tandemly repetitive elements in stromal cells of the TME has been unappreciated, limiting the optimal use of satellite transcripts as biomarkers or anti-cancer targets. We found that transcription of pericentromeric satellite DNA (satDNA) in mouse and human lung adenocarcinoma was observed in cancer-associated fibroblasts (CAFs). In vivo, lung fibroblasts expressed pericentromeric satellite repeats HS2/HS3 specifically in tumors. In vitro, transcription of satDNA was induced in lung fibroblasts in response to TGFβ, IL1α, matrix stiffness, direct contact with tumor cells and treatment with chemotherapeutic drugs. Single-cell transcriptome analysis of human lung adenocarcinoma confirmed that CAFs were the cell type with the highest number of satellite transcripts. Human HS2/HS3 pericentromeric transcripts were detected in the nucleus, cytoplasm, extracellularly and co-localized with extracellular vesicles in situ in human biopsies and activated fibroblasts in vitro. The transcripts were transmitted into recipient cells and entered their nuclei. Knock-down of satellite transcripts in human lung fibroblasts attenuated cellular senescence and blocked the formation of an inflammatory CAFs phenotype which resulted in the inhibition of their pro-tumorigenic functions. In sum, our data suggest that satellite long non-coding (lnc) RNAs are induced in CAFs, regulate expression of inflammatory genes and can be secreted from the cells, which potentially might present a new element of cell-cell communication in the TME.
CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer
Authors: Houthuijzen Julia M. , de Bruijn Roebi , van der Burg Eline , Drenth Anne Paulien , Wientjens Ellen , Filipovic Tamara , Bullock Esme , Brambillasca Chiara S. , Pulver Emilia M. , Nieuwland Marja , de Rink Iris , van Diepen Frank , Klarenbeek Sjoerd , Kerkhoven Ron , Brunton Valerie G. , Scheele Colinda L.G.J. , Boelens Mirjam C. , Jonkers Jos 
Published: January 2023

AbstractCancer-associated fibroblasts (CAFs) are abundantly present in the microenvironment of virtually all tumors and strongly impact tumor progression. Despite increasing insight into their function and heterogeneity, little is known regarding the origin of CAFs. Understanding the origin of CAF heterogeneity is needed to develop successful CAF-based targeted therapies. Through various transplantation studies in mice, we show that CAFs in both invasive lobular breast cancer and triple-negative breast cancer originate from mammary tissue-resident normal fibroblasts (NFs). Single-cell transcriptomics, in vivo and in vitro studies reveal the transition of CD26+ and CD26- NF populations into inflammatory CAFs (iCAFs) and myofibroblastic CAFs (myCAFs), respectively. Functional co-culture experiments show that CD26+ NFs transition into pro-tumorigenic iCAFs which recruit myeloid cells in a CXCL12-dependent manner and enhance tumor cell invasion via matrix-metalloproteinase (MMP) activity. Together, our data suggest that CD26+ and CD26- NFs transform into distinct CAF subpopulations in mouse models of breast cancer.
Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis
Authors: Fankhaenel Maria , Hashemi Farahnaz S. Golestan , Mourao Larissa , Lucas Emily , Hosawi Manal M. , Skipp Paul , Morin Xavier , Scheele Colinda L.G.J. , Elias Salah 
Published: January 2023

AbstractOriented cell divisions are critical for the formation and maintenance of structured epithelia. Proper mitotic spindle orientation relies on polarised anchoring of force generators to the cell cortex by the evolutionarily conserved protein complex formed by the Gαi subunit of heterotrimeric G proteins, the Leucine-Glycine-Asparagine repeat protein (LGN) and the nuclear mitotic apparatus protein. However, the polarity cues that control cortical patterning of this ternary complex remain largely unknown in mammalian epithelia. Here we identify the membrane-associated protein Annexin A1 (ANXA1) as an interactor of LGN in mammary epithelial cells. Annexin A1 acts independently of Gαi to instruct the accumulation of LGN and nuclear mitotic apparatus protein at the lateral cortex to ensure cortical anchoring of Dynein-Dynactin and astral microtubules and thereby planar alignment of the mitotic spindle. Loss of Annexin A1 randomises mitotic spindle orientation, which in turn disrupts epithelial architecture and luminogenesis in three-dimensional cultures of primary mammary epithelial cells. Our findings establish Annexin A1 as an upstream cortical cue that regulates LGN to direct planar cell divisions during mammalian epithelial morphogenesis.
PDGF inhibits BMP2-induced bone healing
Authors: Novak Sanja , Madunic Josip , Shum Laura , Vucetic Milan , Wang Xi , Tanigawa Hitoshi , Ghosh Mallika , Sanjay Archana , Kalajzic Ivo 
Published: January 2023

AbstractBone regeneration depends on a pool of bone/cartilage stem/progenitor cells and signaling mechanisms regulating their differentiation. Using in vitro approach, we have shown that PDGF signaling through PDGFRβ inhibits BMP2-induced osteogenesis, and significantly attenuates expression of BMP2 target genes. We evaluated outcomes of treatment with two anabolic agents, PDGF and BMP2 using different bone healing models. Targeted deletion of PDGFRβ in αSMA osteoprogenitors, led to increased callus bone mass, resulting in improved biomechanical properties of fractures. In critical size bone defects BMP2 treatment increased proportion of osteoprogenitors, while the combined treatment of PDGF BB with BMP2 decreased progenitor number at the injury site. BMP2 treatment induced significant bone formation and increased number of osteoblasts, while in contrast combined treatment with PDGF BB decreased osteoblast numbers. This is in vivo study showing that PDGF inhibits BMP2-induced osteogenesis, but inhibiting PDGF signaling early in healing process does not improve BMP2-induced bone healing.
Ion-tunable antiambipolarity in mixed ion–electron conducting polymers enables biorealistic organic electrochemical neurons
Authors: Harikesh Padinhare Cholakkal , Yang Chi-Yuan , Wu Han-Yan , Zhang Silan , Donahue Mary J. , Caravaca April S. , Huang Jun-Da , Olofsson Peder S. , Berggren Magnus , Tu Deyu , Fabiano Simone 
Published: January 2023

AbstractBiointegrated neuromorphic hardware holds promise for new protocols to record/regulate signalling in biological systems. Making such artificial neural circuits successful requires minimal device/circuit complexity and ion-based operating mechanisms akin to those found in biology. Artificial spiking neurons, based on silicon-based complementary metal-oxide semiconductors or negative differential resistance device circuits, can emulate several neural features but are complicated to fabricate, not biocompatible and lack ion-/chemical-based modulation features. Here we report a biorealistic conductance-based organic electrochemical neuron (c-OECN) using a mixed ion–electron conducting ladder-type polymer with stable ion-tunable antiambipolarity. The latter is used to emulate the activation/inactivation of sodium channels and delayed activation of potassium channels of biological neurons. These c-OECNs can spike at bioplausible frequencies nearing 100 Hz, emulate most critical biological neural features, demonstrate stochastic spiking and enable neurotransmitter-/amino acid-/ion-based spiking modulation, which is then used to stimulate biological nerves in vivo. These combined features are impossible to achieve using previous technologies.
The largest amber-preserved flower revisited
Authors: Sadowski Eva-Maria , Hofmann Christa-Charlotte 
Published: January 2023

AbstractAmber exquisitely preserves the delicate organs of fossil flowers for millions of years. However, flower inclusions can be rare and usually do not exceed 10 mm in size. Here we report an exceptionally large flower from late Eocene Baltic amber, measuring 28 mm across, which is about three times as large as most floral inclusions. This fossil was described over 150 years ago asStewartia kowalewskii(Theaceae) and has never been revised. The analysis of pollen extracted from the anthers of the flower inclusion, however, revealed strong affinities to Asian species ofSymplocos(Symplocaceae), prompting the new combinationSymplocos kowalewskiicomb. nov. et emend. This fossil represents the first record of Symplocaceae from Baltic amber and supports affinities of its flora to evergreen broadleaved and mixed mesophytic forests of present-day East and Southeast Asia. The rarity of such large-sized flower inclusions is likely due to the size of the resin outpouring and its properties, which might affect the embedding of plant organs.
Establishment of quantitative and consistent in vitro skeletal muscle pathological models of myotonic dystrophy type 1 using patient-derived iPSCs
Authors: Kawada Ryu , Jonouchi Tatsuya , Kagita Akihiro , Sato Masae , Hotta Akitsu , Sakurai Hidetoshi 
Published: January 2023

AbstractMyotonic dystrophy type 1 (DM1) is caused by expanded CTG repeats (CTGexp) in the dystrophia myotonica protein kinase (DMPK) gene, and the transcription products, expanded CUG repeats, sequester muscleblind like splicing regulator 1 (MBNL1), resulting in the nuclear MBNL1 aggregation in the DM1 cells. Loss of MBNL1 function is the pivotal mechanism underlying the pathogenesis of DM1. To develop therapeutics for DM1, proper human in vitro models based on the pathologic mechanism of DM1 are required. In this study, we established robust in vitro skeletal muscle cell models of DM1 with patient-derived induced pluripotent stem cells (iPSCs) using the MyoD1-induced system and iPSCs-derived muscle stem cell (iMuSC) differentiation system. Our newly established DM1 models enable simple quantitative evaluation of nuclear MBNL1 aggregation and the downstream splicing defects. Quantitative analyses using the MyoD1-induced myotubes showed that CTGexp-deleted DM1 skeletal myotubes exhibited a reversal of MBNL1-related pathologies, and antisense oligonucleotide treatment recovered these disease phenotypes in the DM1-iPSCs-derived myotubes. Furthermore, iMuSC-derived myotubes exhibited higher maturity than the MyoD1-induced myotubes, which enabled us to recapitulate the SERCA1 splicing defect in the DM1-iMuSC-derived myotubes. Our quantitative and reproducible in vitro models for DM1 established using human iPSCs are promising for drug discovery against DM1.
Effect of metabolic health and obesity on all-cause death and CVD incidence in Korean adults: a retrospective cohort study
Authors: Kim Ye-Seul , Shin Sang-Jun , Kim Yonghwan , Kim Joungyoun , Kang Hee-Taik 
Published: January 2023

AbstractThis study aimed to investigate the risk of all-cause mortality and incidence of CVD according to metabolic health and body mass index (BMI) in Korean adults. This study was retrospectively designed using the National Health Insurance Service-National Health Screening Cohort data. Participants were divided into six groups according to two category of metabolic syndrome and three categories of BMI. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the composite outcome (all-cause mortality and incidence of CVDs) were estimated using multivariable Cox proportional hazards regression models. 151,706 participants aged ≥ 40 years were enrolled; median follow-up period was 9.7 years in the study. Compared to metabolically healthy normal weight, the fully adjusted HRs (95% CIs) of metabolically healthy overweight, metabolically healthy obese, metabolically unhealthy normal weight, metabolically unhealthy overweight, and metabolically unhealthy obese for composite outcome were 1.07 (1.03–1.12), 1.12 (1.07–1.17), 1.33 (1.25–1.41), 1.28 (1.22–1.34), and 1.31 (1.26–1.37), respectively, in men, and 1.10 (1.05–1.16), 1.22 (1.16–1.29), 1.34 (1.26–1.43), 1.27 (1.19–1.34), and, 1.40 (1.34–1.47), respectively, in women. High BMI and metabolic unhealthiness were associated with an increased risk on the composite of all-cause mortality and incidence of CVD in both sexes.
Breast cancer patients from the Midwest region of the United States have reduced levels of short-chain fatty acid-producing gut bacteria
Authors: Shrode Rachel L. , Knobbe Jessica E. , Cady Nicole , Yadav Meeta , Hoang Jemmie , Cherwin Catherine , Curry Melissa , Garje Rohan , Vikas Praveen , Sugg Sonia , Phadke Sneha , Filardo Edward , Mangalam Ashutosh K. 
Published: January 2023

AbstractAs geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the gut microbiome of breast cancer (BC) patients of the Midwestern region of the United States. The bacterial component of the gut microbiome was profiled utilizing 16S ribosomal RNA sequencing. Additionally, a gene pathway analysis was performed to assess the functional capabilities of the bacterial microbiome. Alpha diversity was not significantly different between BC and healthy controls (HC), however beta diversity revealed distinct clustering between the two groups at the species and genera level. Wilcoxon Rank Sum test revealed modulation of several gut bacteria in BC specifically reduced abundance of those linked with beneficial effects such as Faecalibacterium prausnitzii. Machine learning analysis confirmed the significance of several of the modulated bacteria found by the univariate analysis. The functional analysis showed a decreased abundance of SCFA (propionate) production in BC compared to HC. In conclusion, we observed gut dysbiosis in BC with the depletion of SCFA-producing gut bacteria suggesting their role in the pathobiology of breast cancer. Mechanistic understanding of gut bacterial dysbiosis in breast cancer could lead to refined prevention and treatment.
TRAIL mediated apoptosis ruling and anticancer trigger by fine-tuned nano spheres of Fagonia cretica methanolic extracts as novel cancer regime
Authors: Ahmed Warda , Mansoor Qaisar , Ahmad Muhammad Sheeraz , Zainab Tayyaba , Shah Muhammad Ali 
Published: January 2023

AbstractFagonia cretica L. is a tropical plant of family Zygophyllaceae with wide range of medicinally important secondary metabolites. The low cellular uptake of the polar compounds in the extract of the plant limits its biological application. In present study efficacy of F. cretica modified bioactive nano-formulations for in vitro modulation of TRAIL mediated extrinsic apoptotic pathway as cancer therapy was investigated. F. cretica methanolic extracts were formulated at nano-scale for green synthesis of silver nanoparticles, albumin conjugation and liposomes encapsulation to enhance targeted bioactivity against cancer. Physical characterization of the synthesized nanoparticles was done by SEM, EDX and Zeta potential analyzer. In vitro cell viability assay MTT was done for MCF-7, Hep-2, HUH-7 and HCEC cell lines. Relative expression variation of the apoptotic pathway-associated genes was done by qRT-PCR. SEM revealed spherical shape of 56.62 ± 8.04, 143 ± 11.54 and 83.36 ± 38.73 nm size and zeta potential − 18.6, − 15.5 and − 18.3 mV for liposomes, silver and albumin nanoparticles. Silver nanoparticles showed highest anticancer activity in vitro than albumin and liposomes nanoparticles with IC50 0.101 ± 0.004, 0.177 ± 0.03 and 0.434 ± 0.022 mg/mL in MCF-7, Hep-2 and HUH-7 respectively. F. cretica albumin and silver nanoparticles upregulated the in vitro TRAIL, DR4, DR5 and FADD gene expression at statistically significant levels in Hep-2 cell lines. Nano-formulations of F. cretica proved therapeutically important biomolecules in vitro. The hypothesized modulation of extrinsic apoptosis pathway genes through the plant nanoparticles proved novel medicinal options for effective treatment of cancer and enhancing the bioavailability of the active plant metabolites.
A novel pH sensitive theranostic PLGA nanoparticle for boron neutron capture therapy in mesothelioma treatment
Authors: Sforzi Jacopo , Lanfranco Alberto , Stefania Rachele , Alberti Diego , Bitonto Valeria , Parisotto Stefano , Renzi Polyssena , Protti Nicoletta , Altieri Saverio , Deagostino Annamaria , Geninatti Crich Simonetta 
Published: January 2023

AbstractThis study aims to develop poly lactic-co-glycolic acid (PLGA) nanoparticles with an innovative imaging-guided approach based on Boron Neutron Capture Therapy for the treatment of mesothelioma. The herein-reported results demonstrate that PLGA nanoparticles incorporating oligo-histidine chains and the dual Gd/B theranostic agent AT101 can successfully be exploited to deliver a therapeutic dose of boron to mesothelioma cells, significantly higher than in healthy mesothelial cells as assessed by ICP-MS and MRI. The selective release is pH responsive taking advantage of the slightly acidic pH of the tumour extracellular environment and triggered by the protonation of imidazole groups of histidine. After irradiation with thermal neutrons, tumoral and healthy cells survival and clonogenic ability were evaluated. Obtained results appear very promising, providing patients affected by this rare disease with an improved therapeutic option, exploiting PLGA nanoparticles.