bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paralonchothrixgen. nov., the first record of Echimyini (Rodentia, Octodontoidea) in the late Miocene of Southern South America
Authors: PIÑERO Pedro , OLIVARES A. Itatí , VERZI Diego H. , CONTRERAS Victor H. 
Published: July 2021

ABSTRACTEchimyidae is the most widely diversified family among hystricognath rodents, both in the number of species and variety of lifestyles. In the Patagonian Subregion of southern South America, extinct echimyids related to living arboreal species (Echimyini) are recorded up to the middle Miocene, whereas all the known southern fossils since the late Miocene are linked to terrestrial and fossorial lineages currently inhabiting the Chacoan open biome in eastern South America. In this work, we describe a new genus of echimyid rodent,Paralonchothrixgen. nov., from the late Miocene of northwestern Argentina and western Brazil. Its single recognised species,Paralonchothrix ponderosuscomb. nov., is represented by two hemimandibles. One of them comes from a level of Loma de Las Tapias Formation, underlying a tuff dated at 7.0 ± 0.9 Ma (Huayquerian age, late Miocene); the other specimen comes from the ‘Araucanense’ of Valle de Santa María (type locality, Huayquerian age, late Miocene). A phylogenetic analysis linkedParalonchothrixtoLonchothrix, both being the sister group toMesomys. Thereby, for the first time, an echimyid linked to living Amazonian arboreal clades is recognised for the late Miocene of southern South America.Paralonchothrixgen. nov. thus represents an exceptional record that raises the need to review the postulated evolutionary pattern for echimyids recorded at high latitudes since the late Miocene. The new genus provides a minimum age (ca.7 Ma) in the fossil record for the divergence betweenMesomysandLonchothrix. The palaeoenvironmental conditions inferred for the late Miocene in western and northwestern Argentina suggest savanna-type environments, with areas with more closed woodlands in peri-Andean valleys. The record ofParalonchothrixgen. nov. supports the hypothesis that this area would have maintained connections with tropical biomes of northern South America during the late Miocene.
Drift Velocity Estimation of Ionospheric Bubbles Using GNSS Observations
Authors: Souza Ana L. C. , Camargo Paulo O. , Muella Marcio T. A. H. , Tardelli‐Coelho Flavia 
Published: July 2021

AbstractEquatorial plasma bubble (EPB) irregularities are large‐scale plasma depleted structures that exist in the equatorial and low‐latitude ionosphere. Thus, particularly in these regions, much attention must be given to the effects of the EPBs in the life critical applications based on global navigation satellite systems (GNSS). The study on the dynamics of plasma bubbles, particularly in the determination of their drift velocities, and their impact on ground‐based augmentation system is of fundamental importance for civilian aviation. In this regard, we proposed a methodology to estimate the zonal drift velocities of the plasma bubble irregularities using slant total electron content (TEC) measurements derived from two spaced ground‐based GNSS receivers. The experiments were performed with the purpose to evaluate if the drift velocities obtained using the methodology proposed in this study agree with the velocities deduced from all‐sky imaging systems. The results revealed that the TEC‐estimated mean eastward drift velocities were comparable with the values deduced from the airglow techniques, and with the results obtained from previous studies. Therefore, the methodology proposed in this work to infer the plasma bubble drift velocities seem to have the potential in future investigations to provide a new data source in this field.
NASA CERES Spurious Calibration Drifts Corrected by Lunar Scans to Show the Sun Is not Increasing Global Warming and Allow Immediate CRF Detection
Authors: Matthews Grant 
Published: July 2021

AbstractOrbital Earth Radiation Budget measurement comparisons to models, are critical for climate prediction confidence. Satellite systems must reduce calibration drifts for this purpose. NASA Clouds and the Earth's Radiant Energy System (CERES) measures Earth albedo reductions that if correct, would increase solar forcing and suggest greater sunlight absorption is driving much of recent temperature increases. Such results are presented, alongside those from the Moon and Earth Radiation Budget Experiment (MERBE). MERBE uses constant lunar reflectivity for tracking and compensation of instrument telescope degradation, undetectable by CERES. MERBE finds Earth albedo constant compared to that of the Moon, because Arctic solar warming effects are balanced by solar cooling elsewhere, likely due to negative feedbacks. Contrary to NASA, this shows the Sun is not increasing warming and that CERES results are not as stable as claimed and assumed. Furthermore, MERBE can actually resolve Cloud Radiative Forcing (CRF) signals from the existing record, rather than in decades with official observations.
Lactate secreted by PKM2 upregulation promotes Galectin-9-mediated immunosuppression via inhibiting NF-κB pathway in HNSCC
Authors: Chang Hanyue , Xu Qiaoshi , Li Jiayi , Li Mingyu , Zhang Zhiyuan , Ma Hailong , Yang Xi 
Published: July 2021

AbstractPyruvate kinase M2 as a key rate-limiting enzyme in glycolysis, it plays a critical role in metabolic reprogramming and carcinogenesis. However, whether PKM2 can promote immunosuppressive microenvironment formation remains unknown in head and neck squamous cell carcinoma (HNSCC). PKM2 expression was detected using immunohistochemical staining. The biological functions of PKM2 were investigated in vitro and in vivo. Lactate production and the expression of Galectin-9, a critical immunosuppression molecule, were detected after PKM2 knockdown and overexpression in HNSCC cells. The mechanism of lactate regulating Galectin-9 expression through NF-κB signaling was explored in vitro. Overexpression of PKM2 correlates with poor prognosis in HNSCC patients. Silencing PKM2 markedly inhibits proliferation and metastasis capacity in vivo and in vitro, and vice versa. The glycolysis and glycolytic capacity are significantly decreased after PKM2 silencing. Lactate secretion induced by PKM2 significantly promotes migration and invasion capacity. Furthermore, a positive correlation between PKM2 and Galectin-9 expression is observed in HNSCC tissues. The induction of Galectin-9 expression by PKM2 can be affected by a lactate transporter inhibitor. Mechanically, lactate impeded the suppressive transcriptional complex formation of NF-κB and histone deacetylase 3 (HDAC3), which released the transcription of Galectin-9 mediated by NF-κB signaling. Our findings demonstrate that lactate produced by PKM2 upregulation promotes tumor progression and Galectin-9-mediated immunosuppression via NF-κB signaling inhibition in HNSCC, which bridges metabolism and immunosuppression. The novel PKM2-lactate-Galectin-9 axis might be a potential therapeutic target in HNSCC.
Genome-wide CRISPR/Cas9 screening identifies CARHSP1 responsible for radiation resistance in glioblastoma
Authors: Zhu Guo-dong , Yu Jing , Sun Zheng-yu , Chen Yan , Zheng Hong-mei , Lin Mei-lan , Ou-yang Shi , Liu Guo-long , Zhang Jie-wen , Shao Feng-min 
Published: July 2021

AbstractGlioblastomas (GBM) is the most common primary malignant brain tumor, and radiotherapy plays a critical role in its therapeutic management. Unfortunately, the development of radioresistance is universal. Here, we identified calcium-regulated heat-stable protein 1 (CARHSP1) as a critical driver for radioresistance utilizing genome-wide CRISPR activation screening. This is a protein with a cold-shock domain (CSD)-containing that is highly similar to cold-shock proteins. CARHSP1 mRNA level was upregulated in irradiation-resistant GBM cells and knockdown of CARHSP1 sensitized GBM cells to radiotherapy. The high expression of CARHSP1 upon radiation might mediate radioresistance by activating the inflammatory signaling pathway. More importantly, patients with high levels of CARHSP1 had poorer survival when treated with radiotherapy. Collectively, our findings suggested that targeting the CARHSP1/TNF-α inflammatory signaling activation induced by radiotherapy might directly affect radioresistance and present an attractive therapeutic target for GBM, particularly for patients with high levels of CARHSP1.
A single-amino-acid in-frame deletion in CYP17A1 results in combined 17-hydroxylase and 17,20-lyase deficiency in an Iranian family despite the protein mutation site
Authors: Habib Ashkan , Shojazadeh Alireza , Molayemat Mohadeseh , Jafari Khamirani Hossein , Zoghi Sina , Dastgheib Seyed Alireza , Habib Asadollah 
Published: July 2021

AbstractIn this study, we detected homozygous mutations in the CYP17A1 gene (NM_000102.4:c.1053_1055delCCT; p.Leu353del; SCV001479329) in a 28-year-old female patient (46,XX) and her phenotypically female 30-year-old sister (46,XY) who had phenotypes consistent with combined 17-hydroxylase and 17,20-lyase deficiency. The phenotypes were not expected based on the location of the mutation in the CYP17A1 redox partner-binding site and a previous description of the same mutation linked with isolated 17,20-lyase deficiency.
Distinct cortical systems reinstate the content and context of episodic memories
Authors: Kragel James E. , Ezzyat Youssef , Lega Bradley C. , Sperling Michael R. , Worrell Gregory A. , Gross Robert E. , Jobst Barbara C. , Sheth Sameer A. , Zaghloul Kareem A. , Stein Joel M. , Kahana Michael J. 
Published: July 2021

AbstractEpisodic recall depends upon the reinstatement of cortical activity present during the formation of a memory. Evidence from functional neuroimaging and invasive recordings in humans suggest that reinstatement organizes our memories by time or content, yet the neural systems involved in reinstating these unique types of information remain unclear. Here, combining computational modeling and intracranial recordings from 69 epilepsy patients, we show that two cortical systems uniquely reinstate the semantic content and temporal context of previously studied items during free recall. Examining either the posterior medial or anterior temporal networks, we find that forward encoding models trained on the brain’s response to the temporal and semantic attributes of items can predict the serial position and semantic category of unseen items. During memory recall, these models uniquely link reinstatement of temporal context and semantic content to these posterior and anterior networks, respectively. These findings demonstrate how specialized cortical systems enable the human brain to target specific memories.
Reactivation of a developmentally silenced embryonic globin gene
Authors: King Andrew J. , Songdej Duantida , Downes Damien J. , Beagrie Robert A. , Liu Siyu , Buckley Megan , Hua Peng , Suciu Maria C. , Marieke Oudelaar A. , Hanssen Lars L. P. , Jeziorska Danuta , Roberts Nigel , Carpenter Stephanie J. , Francis Helena , Telenius Jelena , Olijnik Aude-Anais , Sharpe Jacqueline A. , Sloane-Stanley Jacqueline , Eglinton Jennifer , Kassouf Mira T. , Orkin Stuart H. , Pennacchio Len A. , Davies James O. J. , Hughes Jim R. , Higgs Douglas R. , Babbs Christian 
Published: July 2021

AbstractThe α- and β-globin loci harbor developmentally expressed genes, which are silenced throughout post-natal life. Reactivation of these genes may offer therapeutic approaches for the hemoglobinopathies, the most common single gene disorders. Here, we address mechanisms regulating the embryonically expressed α-like globin, termed ζ-globin. We show that in embryonic erythroid cells, the ζ-gene lies within a ~65 kb sub-TAD (topologically associating domain) of open, acetylated chromatin and interacts with the α-globin super-enhancer. By contrast, in adult erythroid cells, the ζ-gene is packaged within a small (~10 kb) sub-domain of hypoacetylated, facultative heterochromatin within the acetylated sub-TAD and that it no longer interacts with its enhancers. The ζ-gene can be partially re-activated by acetylation and inhibition of histone de-acetylases. In addition to suggesting therapies for severe α-thalassemia, these findings illustrate the general principles by which reactivation of developmental genes may rescue abnormalities arising from mutations in their adult paralogues.
Temporal stability of stimulus representation increases along rodent visual cortical hierarchies
Authors: Piasini Eugenio , Soltuzu Liviu , Muratore Paolo , Caramellino Riccardo , Vinken Kasper , Op de Beeck Hans , Balasubramanian Vijay , Zoccolan Davide 
Published: July 2021

AbstractCortical representations of brief, static stimuli become more invariant to identity-preserving transformations along the ventral stream. Likewise, increased invariance along the visual hierarchy should imply greater temporal persistence of temporally structured dynamic stimuli, possibly complemented by temporal broadening of neuronal receptive fields. However, such stimuli could engage adaptive and predictive processes, whose impact on neural coding dynamics is unknown. By probing the rat analog of the ventral stream with movies, we uncovered a hierarchy of temporal scales, with deeper areas encoding visual information more persistently. Furthermore, the impact of intrinsic dynamics on the stability of stimulus representations grew gradually along the hierarchy. A database of recordings from mouse showed similar trends, additionally revealing dependencies on the behavioral state. Overall, these findings show that visual representations become progressively more stable along rodent visual processing hierarchies, with an important contribution provided by intrinsic processing.
Ageing is associated with disrupted reinforcement learning whilst learning to help others is preserved
Authors: Cutler Jo , Wittmann Marco K. , Abdurahman Ayat , Hargitai Luca D. , Drew Daniel , Husain Masud , Lockwood Patricia L. 
Published: July 2021

AbstractReinforcement learning is a fundamental mechanism displayed by many species. However, adaptive behaviour depends not only on learning about actions and outcomes that affect ourselves, but also those that affect others. Using computational reinforcement learning models, we tested whether young (age 18–36) and older (age 60–80, total n = 152) adults learn to gain rewards for themselves, another person (prosocial), or neither individual (control). Detailed model comparison showed that a model with separate learning rates for each recipient best explained behaviour. Young adults learned faster when their actions benefitted themselves, compared to others. Compared to young adults, older adults showed reduced self-relevant learning rates but preserved prosocial learning. Moreover, levels of subclinical self-reported psychopathic traits (including lack of concern for others) were lower in older adults and the core affective-interpersonal component of this measure negatively correlated with prosocial learning. These findings suggest learning to benefit others is preserved across the lifespan with implications for reinforcement learning and theories of healthy ageing.
Superconductivity in an extreme strange metal
Authors: Nguyen D. H. , Sidorenko A. , Taupin M. , Knebel G. , Lapertot G. , Schuberth E. , Paschen S. 
Published: July 2021

AbstractSome of the highest-transition-temperature superconductors across various materials classes exhibit linear-in-temperature ‘strange metal’ or ‘Planckian’ electrical resistivities in their normal state. It is thus believed by many that this behavior holds the key to unlock the secrets of high-temperature superconductivity. However, these materials typically display complex phase diagrams governed by various competing energy scales, making an unambiguous identification of the physics at play difficult. Here we use electrical resistivity measurements into the micro-Kelvin regime to discover superconductivity condensing out of an extreme strange metal state—with linear resistivity over 3.5 orders of magnitude in temperature. We propose that the Cooper pairing is mediated by the modes associated with a recently evidenced dynamical charge localization–delocalization transition, a mechanism that may well be pertinent also in other strange metal superconductors.
Above- and belowground biodiversity jointly tighten the P cycle in agricultural grasslands
Authors: Oelmann Yvonne , Lange Markus , Leimer Sophia , Roscher Christiane , Aburto Felipe , Alt Fabian , Bange Nina , Berner Doreen , Boch Steffen , Boeddinghaus Runa S. , Buscot François , Dassen Sigrid , De Deyn Gerlinde , Eisenhauer Nico , Gleixner Gerd , Goldmann Kezia , Hölzel Norbert , Jochum Malte , Kandeler Ellen , Klaus Valentin H. , Kleinebecker Till , Le Provost Gaëtane , Manning Peter , Marhan Sven , Prati Daniel , Schäfer Deborah , Schöning Ingo , Schrumpf Marion , Schurig Elisabeth , Wagg Cameron , Wubet Tesfaye , Wilcke Wolfgang 
Published: July 2021

AbstractExperiments showed that biodiversity increases grassland productivity and nutrient exploitation, potentially reducing fertiliser needs. Enhancing biodiversity could improve P-use efficiency of grasslands, which is beneficial given that rock-derived P fertilisers are expected to become scarce in the future. Here, we show in a biodiversity experiment that more diverse plant communities were able to exploit P resources more completely than less diverse ones. In the agricultural grasslands that we studied, management effects either overruled or modified the driving role of plant diversity observed in the biodiversity experiment. Nevertheless, we show that greater above- (plants) and belowground (mycorrhizal fungi) biodiversity contributed to tightening the P cycle in agricultural grasslands, as reduced management intensity and the associated increased biodiversity fostered the exploitation of P resources. Our results demonstrate that promoting a high above- and belowground biodiversity has ecological (biodiversity protection) and economical (fertiliser savings) benefits. Such win-win situations for farmers and biodiversity are crucial to convince farmers of the benefits of biodiversity and thus counteract global biodiversity loss.
Neonatal thyroxine activation modifies epigenetic programming of the liver
Authors: Fonseca Tatiana L. , Garcia Tzintzuni , Fernandes Gustavo W. , Nair T. Murlidharan , Bianco Antonio C. 
Published: July 2021

AbstractThe type 2 deiodinase (D2) in the neonatal liver accelerates local thyroid hormone triiodothyronine (T3) production and expression of T3-responsive genes. Here we show that this surge in T3 permanently modifies hepatic gene expression. Liver-specific Dio2 inactivation (Alb-D2KO) transiently increases H3K9me3 levels during post-natal days 1–5 (P1–P5), and results in methylation of 1,508 DNA sites (H-sites) in the adult mouse liver. These sites are associated with 1,551 areas of reduced chromatin accessibility (RCA) within core promoters and 2,426 within intergenic regions, with reduction in the expression of 1,363 genes. There is strong spatial correlation between density of H-sites and RCA sites. Chromosome conformation capture (Hi-C) data reveals a set of 81 repressed genes with a promoter RCA in contact with an intergenic RCA ~300 Kbp apart, within the same topologically associating domain (χ2 = 777; p < 0.00001). These data explain how the systemic hormone T3 acts locally during development to define future expression of hepatic genes.
A human CD137×PD-L1 bispecific antibody promotes anti-tumor immunity via context-dependent T cell costimulation and checkpoint blockade
Authors: Geuijen Cecile , Tacken Paul , Wang Liang-Chuan , Klooster Rinse , van Loo Pieter Fokko , Zhou Jing , Mondal Arpita , Liu Yao-bin , Kramer Arjen , Condamine Thomas , Volgina Alla , Hendriks Linda J. A. , van der Maaden Hans , Rovers Eric , Engels Steef , Fransen Floris , den Blanken-Smit Renate , Zondag-van der Zande Vanessa , Basmeleh Abdul , Bartelink Willem , Kulkarni Ashwini , Marissen Wilfred , Huang Cheng-Yen , Hall Leslie , Harvey Shane , Kim Soyeon , Martinez Marina , O’Brien Shaun , Moon Edmund , Albelda Steven , Kanellopoulou Chrysi , Stewart Shaun , Nastri Horacio , Bakker Alexander B. H. , Scherle Peggy , Logtenberg Ton , Hollis Gregory , de Kruif John , Huber Reid , Mayes Patrick A. , Throsby Mark 
Published: July 2021

AbstractImmune checkpoint inhibitors demonstrate clinical activity in many tumor types, however, only a fraction of patients benefit. Combining CD137 agonists with these inhibitors increases anti-tumor activity preclinically, but attempts to translate these observations to the clinic have been hampered by systemic toxicity. Here we describe a human CD137xPD-L1 bispecific antibody, MCLA-145, identified through functional screening of agonist- and immune checkpoint inhibitor arm combinations. MCLA-145 potently activates T cells at sub-nanomolar concentrations, even under suppressive conditions, and enhances T cell priming, differentiation and memory recall responses. In vivo, MCLA-145 anti-tumor activity is superior to immune checkpoint inhibitor comparators and linked to recruitment and intra-tumor expansion of CD8 + T cells. No graft-versus-host-disease is observed in contrast to other antibodies inhibiting the PD-1 and PD-L1 pathway. Non-human primates treated with 100 mg/kg/week of MCLA-145 show no adverse effects. The conditional activation of CD137 signaling by MCLA-145, triggered by neighboring cells expressing >5000 copies of PD-L1, may provide both safety and potency advantages.
Case-control study of hypertension and Parkinson’s disease
Authors: Ng Yuen-Fann , Ng Ebonne , Lim Ee-Wei , Prakash Kumar M. , Tan Louis C. S. , Tan Eng-King 
Published: July 2021

AbstractWe evaluate the association of hypertension with PD in an Asian population and performed a meta-analysis on similar studies to address the effect of hypertension on PD risk. A matched case-control study involving 1342 Chinese subjects (671 PD and 671 age and gender-matched controls (with a mean age of 63.9 ± 9.7 and 63.5 ± 9.8 years, and identical proportion of gender distribution) was conducted. Hypertension increases PD risk by 1.9 times [OR 1.86 (1.46–2.38)]. The literature search identified 618 studies initially; however, only three matched case-control studies (all in Caucasians) met the inclusion criteria for meta-analysis. Overall analysis showed that hypertension decreases PD risk by 0.2 times [OR 0.80 (0.66–0.96)]. Hypertension increases PD risk by 1.9 times in our Asian population. However, a meta-analysis comprising of Caucasian populations showed a protective effect of hypertension suggesting that ethnic differences or other genetic or environmental factors may contribute to the divergent observation. Early diagnosis and treatment of hypertension may potentially reduce the risk of PD, at least in our population.