bluuebunny/crossref_metadata_2025_split huggingface dataset:
Near‐Surface Stratification Due to Ice Melt Biases Arctic Air‐Sea CO2 Flux Estimates
Authors: Dong Yuanxu , Yang Mingxi , Bakker Dorothee C. E. , Liss Peter S. , Kitidis Vassilis , Brown Ian , Chierici Melissa , Fransson Agneta , Bell Thomas G. 
Published: November 2021

AbstractAir‐sea carbon dioxide (CO2) flux is generally estimated by the bulk method using upper ocean CO2 fugacity measurements. In the summertime Arctic, sea‐ice melt results in stratification within the upper ocean (top ∼10 m), which can bias bulk CO2 flux estimates when the seawater CO2 fugacity is taken from a ship's seawater inlet at ∼6 m depth (fCO2w_bulk). Direct flux measurements by eddy covariance are unaffected by near‐surface stratification. We use eddy covariance CO2 flux measurements to infer sea surface CO2 fugacity (fCO2w_surface) in the Arctic Ocean. In sea‐ice melt regions, fCO2w_surface values are consistently lower than fCO2w_bulk by an average of 39 μatm. Lower fCO2w_surface can be partially accounted for by fresher (≥27%) and colder (17%) melt waters. A back‐of‐the‐envelope calculation shows that neglecting the summertime sea‐ice melt could lead to a 6%–17% underestimate of the annual Arctic Ocean CO2 uptake.
First Measurements of Surface Nuclear Magnetic Resonance Signals Without an Oscillating Excitation Pulse – Exploiting Non‐Adiabatic Prepolarization Switch‐Off
Authors: Hiller Thomas , Costabel Stephan , Dlugosch Raphael , Müller‐Petke Mike 
Published: November 2021

AbstractRecently, small‐scale surface nuclear magnetic resonance (SNMR) measurements with a footprint of about a few square meters have gained interest in the soil geophysics community as they directly provide water content and pore geometry information. Here, the application of strong prepolarization (PP) fields enables the detection of water in the vadose zone. Introducing PP into SNMR shifts the reference for the decay of the SNMR signal from the excitation pulse to the end of the PP, effectively increasing the instrumental dead time, which is already too long to measure short signals associated with unsaturated fine‐grained soil. In an approach to overcome this limitation, we present the first measurements of SNMR signals from a water reservoir without an oscillating excitation pulse. Instead, we use the non‐adiabatic, that is, imperfect, switch‐off of the PP‐field as an effective excitation mechanism. We complement our field experiments with numerical simulations of the corresponding SNMR spin dynamics.
Using Radiative Convective Equilibrium to Explore Clouds and Climate in the Community Atmosphere Model
Authors: Reed Kevin A. , Silvers Levi G. , Wing Allison A. , Hu I‐Kuan , Medeiros Brian 
Published: November 2021

AbstractCharacteristics of, and fundamental differences between, the radiative‐convective equilibrium (RCE) climate states following the Radiative‐Convective Equilibrium Model Intercomparison Project (RCEMIP) protocols in the Community Atmosphere Model version 5 (CAM5) and version 6 (CAM6) are presented. This paper explores the characteristics of clouds, moisture, precipitation and circulation in the RCE state, as well as the tropical response to surface warming, in CAM5 and CAM6 with different parameterizations. Overall, CAM5 simulates higher precipitation rates that result in larger global average precipitation, despite lower outgoing longwave radiation compared to CAM6. Differences in the structure of clouds, particularly the amount and vertical location of cloud liquid, exist between the CAM versions and can, in part, be related to distinct representations of shallow convection and boundary layer processes. Both CAM5 and CAM6 simulate similar peaks in cloud fraction, relative humidity, and cloud ice, linked to the usage of a similar deep convection parameterization. These anvil clouds rise and decrease in extent in response to surface warming. More generally, extreme precipitation, aggregation of convection, and climate sensitivity increase with warming in both CAM5 and CAM6. This analysis provides a benchmark for future studies that explore clouds, convection, and climate in CAM with the RCEMIP protocols now available in the Community Earth System Model. These results are discussed within the context of realistic climate simulations using CAM5 and CAM6, highlighting the usefulness of a hierarchical modeling approach to understanding model and parameterization sensitivities to inform model development efforts.
Modeling clonal hematopoiesis in umbilical cord blood cells by CRISPR/Cas9
Authors: Christen Friederike , Hablesreiter Raphael , Hoyer Kaja , Hennch Cornelius , Maluck-Böttcher Antje , Segler Angela , Madadi Annett , Frick Mareike , Bullinger Lars , Briest Franziska , Damm Frederik 
Published: November 2021

AbstractTo investigate clonal hematopoiesis associated gene mutations in vitro and to unravel the direct impact on the human stem and progenitor cell (HSPC) compartment, we targeted healthy, young hematopoietic progenitor cells, derived from umbilical cord blood samples, with CRISPR/Cas9 technology. Site-specific mutations were introduced in defined regions of DNMT3A, TET2, and ASXL1 in CD34+ progenitor cells that were subsequently analyzed in short-term as well as long-term in vitro culture assays to assess self-renewal and differentiation capacities. Colony-forming unit (CFU) assays revealed enhanced self-renewal of TET2 mutated (TET2mut) cells, whereas ASXL1mut as well as DNMT3Amut cells did not reveal significant changes in short-term culture. Strikingly, enhanced colony formation could be detected in long-term culture experiments in all mutants, indicating increased self-renewal capacities. While we could also demonstrate preferential clonal expansion of distinct cell clones for all mutants, the clonal composition after long-term culture revealed a mutation-specific impact on HSPCs. Thus, by using primary umbilical cord blood cells, we were able to investigate epigenetic driver mutations without confounding factors like age or a complex mutational landscape, and our findings provide evidence for a direct impact of clonal hematopoiesis-associated mutations on self-renewal and clonal composition of human stem and progenitor cells.
Iron overload in endometriosis peritoneal fluid induces early embryo ferroptosis mediated by HMOX1
Authors: Li Shishi , Zhou Yier , Huang Qiongxiao , Fu Xiaohua , Zhang Ling , Gao Fang , Jin Zhen , Wu Limei , Shu Chongyi , Zhang Xirong , Xu Weihai , Shu Jing 
Published: November 2021

AbstractEndometriosis is one of the most common disorders that causes infertility in women. Iron is overloaded in endometriosis peritoneal fluid (PF), with harmful effects on early embryo development. However, the mechanism by which endometriosis peritoneal fluid affects embryonic development remains unclear. Hence, this study investigated the effect of iron overload on mouse embryos and elucidated the molecular mechanism. Iron overload in endometriosis PF disrupted blastocyst formation, decreased GPX4 expression and induced lipid peroxidation, suggesting that iron overload causes embryotoxicity and induces ferroptosis. Moreover, mitochondrial damage occurs in iron overload-treated embryos, presenting as decreased ATP levels, increased ROS levels and MMP hyperpolarization. The cytotoxicity of iron overload is attenuated by the ferroptosis inhibitor Fer-1. Furthermore, Smart-seq analysis revealed that HMOX1 is upregulated in embryo ferroptosis and that HMOX1 suppresses ferroptosis by maintaining mitochondrial function. This study provides new insight into the mechanism of endometriosis infertility and a potential target for future endometriosis infertility treatment efforts.
Zipper head mechanism of telomere synthesis by human telomerase
Authors: Wan Futang , Ding Yongbo , Zhang Yuebin , Wu Zhenfang , Li Shaobai , Yang Lin , Yan Xiangyu , Lan Pengfei , Li Guohui , Wu Jian , Lei Ming 
Published: November 2021

AbstractTelomerase, a multi-subunit ribonucleoprotein complex, is a unique reverse transcriptase that catalyzes the processive addition of a repeat sequence to extend the telomere end using a short fragment of its own RNA component as the template. Despite recent structural characterizations of human and Tetrahymena telomerase, it is still a mystery how telomerase repeatedly uses its RNA template to synthesize telomeric DNA. Here, we report the cryo-EM structure of human telomerase holoenzyme bound with telomeric DNA at resolutions of 3.5 Å and 3.9 Å for the catalytic core and biogenesis module, respectively. The structure reveals that a leucine residue Leu980 in telomerase reverse transcriptase (TERT) catalytic subunit functions as a zipper head to limit the length of the short primer–template duplex in the active center. Moreover, our structural and computational analyses suggest that TERT and telomerase RNA (hTR) are organized to harbor a preformed active site that can accommodate short primer–template duplex substrates for catalysis. Furthermore, our findings unveil a double-fingers architecture in TERT that ensures nucleotide addition processivity of human telomerase. We propose that the zipper head Leu980 is a structural determinant for the sequence-based pausing signal of DNA synthesis that coincides with the RNA element-based physical template boundary. Functional analyses unveil that the non-glycine zipper head plays an essential role in both telomerase repeat addition processivity and telomere length homeostasis. In addition, we also demonstrate that this zipper head mechanism is conserved in all eukaryotic telomerases. Together, our study provides an integrated model for telomerase-mediated telomere synthesis.
Untangling the clinicopathological significance of MRE11-RAD50-NBS1 complex in sporadic breast cancers
Authors: Alblihy Adel , Shoqafi Ahmed , Toss Michael S. , Algethami Mashael , Harris Anna E. , Jeyapalan Jennie N. , Abdel-Fatah Tarek , Servante Juliette , Chan Stephen Y. T. , Green Andrew , Mongan Nigel P. , Rakha Emad A. , Madhusudan Srinivasan 
Published: November 2021

AbstractThe MRE11–RAD50–NBS1 (MRN) complex is critical for genomic stability. Although germline mutations in MRN may increase breast cancer susceptibility, such mutations are extremely rare. Here, we have conducted a comprehensive clinicopathological study of MRN in sporadic breast cancers. We have protein expression profiled for MRN and a panel of DNA repair factors involved in double-strand break repair (BRCA1, BRCA2, ATM, CHK2, ATR, Chk1, pChk1, RAD51, γH2AX, RPA1, RPA2, DNA-PKcs), RECQ DNA helicases (BLM, WRN, RECQ1, RECQL4, RECQ5), nucleotide excision repair (ERCC1) and base excision repair (SMUG1, APE1, FEN1, PARP1, XRCC1, Pol β) in 1650 clinical breast cancers. The prognostic significance of MRE11, RAD50 and NBS1 transcripts and their microRNA regulators (hsa-miR-494 and hsa-miR-99b) were evaluated in large clinical datasets. Expression of MRN components was analysed in The Cancer Genome Atlas breast cancer cohort. We show that low nuclear MRN is linked to aggressive histopathological phenotypes such as high tumour grade, high mitotic index, oestrogen receptor- and high-risk Nottingham Prognostic Index. In univariate analysis, low nuclear MRE11 and low nuclear RAD50 were associated with poor survival. In multivariate analysis, low nuclear RAD50 remained independently linked with adverse clinical outcomes. Low RAD50 transcripts were also linked with reduced survival. In contrast, overexpression of hsa-miR-494 and hsa-miR-99b microRNAs was associated with poor survival. We observed large-scale genome-wide alterations in MRN-deficient tumours contributing to aggressive behaviour. We conclude that MRN status may be a useful tool to stratify tumours for precision medicine strategies.
Pathogenic neurofibromatosis type 1 (NF1) RNA splicing resolved by targeted RNAseq
Authors: Koster R. , Brandão R. D. , Tserpelis D. , van Roozendaal C. E. P. , van Oosterhoud C. N. , Claes K. B. M. , Paulussen A. D. C. , Sinnema M. , Vreeburg M. , van der Schoot V. , Stumpel C. T. R. M. , Broen M. P. G. , Spruijt L. , Jongmans M. C. J. , Lesnik Oberstein S. A. J. , Plomp A. S. , Misra-Isrie M. , Duijkers F. A. , Louwers M. J. , Szklarczyk R. , Derks K. W. J. , Brunner H. G. , van den Wijngaard A. , van Geel M. , Blok M. J. 
Published: November 2021

AbstractNeurofibromatosis type 1 (NF1) is caused by loss-of-function variants in the NF1 gene. Approximately 10% of these variants affect RNA splicing and are either missed by conventional DNA diagnostics or are misinterpreted by in silico splicing predictions. Therefore, a targeted RNAseq-based approach was designed to detect pathogenic RNA splicing and associated pathogenic DNA variants. For this method RNA was extracted from lymphocytes, followed by targeted RNAseq. Next, an in-house developed tool (QURNAs) was used to calculate the enrichment score (ERS) for each splicing event. This method was thoroughly tested using two different patient cohorts with known pathogenic splice-variants in NF1. In both cohorts all 56 normal reference transcript exon splice junctions, 24 previously described and 45 novel non-reference splicing events were detected. Additionally, all expected pathogenic splice-variants were detected. Eleven patients with NF1 symptoms were subsequently tested, three of which have a known NF1 DNA variant with a putative effect on RNA splicing. This effect could be confirmed for all 3. The other eight patients were previously without any molecular confirmation of their NF1-diagnosis. A deep-intronic pathogenic splice variant could now be identified for two of them (25%). These results suggest that targeted RNAseq can be successfully used to detect pathogenic RNA splicing variants in NF1.
The effects of subliminal or supraliminal sadness induction on the sense of body ownership and the role of dissociative symptoms
Authors: Schroter Franziska A. , Günther Bianca A. , Jansen Petra 
Published: November 2021

AbstractPrevious research has shown that emotions can alter our sense of ownership. Whether this relationship is modulated by differences in emotion experience and awareness, however, remains unclear. We investigated this by comparing the susceptibility to the rubber hand illusion (RHI) between participants who were either exposed to a low-arousing emotion induction (sadness) or placed in a neutral control group. Several factors that might influence this relationship were considered: dissociative symptoms were included to observe if a sadness induction led to a higher RHI score in participants scoring high in dissociation, as a result of detached emotion experience. Whether the level of awareness of the emotion mattered was also tested, as subliminal processing was shown to require less focal attention. Therefore, our sample (N = 122) was divided into three experimental groups: Sad pictures were presented to two of the three groups differing in presentation mode (subliminal: n = 40, supraliminal: n = 41), neutral pictures were presented supraliminally to the control group (n = 41). Additionally, the effects of slow (3 cm/s) and fast (30 cm/s) stroking, applied either synchronously or asynchronously, were examined as the comforting effects of stroking might interfere with the emotion induction. Results showed that the supraliminal sadness induction was associated with a stronger subjective illusion, but not with a higher proprioceptive drift compared to the subliminal induction. In addition, a stronger subjective illusion after fast and synchronous stroking was found compared to slow and asynchronous stroking. A significant proprioceptive drift was detected independent of group and stroking style. Both slow and synchronous stroking were perceived as more comforting than their respective counterparts. Participants with higher dissociative symptoms were more susceptible to the subjective illusion, especially in the supraliminal group in the synchronous condition. We concluded that individual differences in emotion experience are likely to play a role in body ownership. However, we cannot clarify at this stage whether differences in proprioception and the subjective illusion depend on the type of emotion experienced (e.g. different levels of arousal) and on concomitant changes in multisensory integration processes.
Lion and spotted hyena distributions within a buffer area of the Serengeti-Mara ecosystem
Authors: Mwampeta Stanslaus B. , Wilton Clay M. , Mkasanga Imani J. , Masinde Lusato M. , Ranke Peter S. , Røskaft Eivin , Fyumagwa Robert , Belant Jerrold L. 
Published: November 2021

AbstractMost large carnivore populations are declining due to anthropogenic activities including direct persecution, prey depletion, habitat loss and degradation. protected areas (PAs) can help maintain viable large carnivore populations; however, anthropogenic activities occurring near and within PA borders or edges can reduce their effectiveness. We investigated the influence of edge effects on abundance of lions (Panthera leo) and spotted hyenas (Crocuta crocuta) in Maswa Game Reserve (MGR), a part of the Serengeti ecosystem in northern Tanzania. We conducted repeated call-ins to attract and enumerate lions and hyenas at 20 stations in MGR during June–July 2017. We used N-mixture models to estimate hyena and lion abundance in relation to land cover and distance from the south-western MGR borders which are adjacent to villages. We found lowest lion and hyena abundances by the south-western border, with abundance of both species increasing toward the eastern border adjacent to Serengeti National Park. Lions were uniformly distributed among land covers whereas hyenas were more abundant in woodlands. We suggest that reduced lion and hyena abundance near human settlements was in response to depleted prey, due to human actions. We recommend ecologically compatible land uses and effective border patrols to mitigate these adverse effects.
Formulas and algorithms for the length of a Farey sequence
Authors: Sukhoy Vladimir , Stoytchev Alexander 
Published: November 2021

AbstractThis paper proves several novel formulas for the length of a Farey sequence of order n. The formulas use different trade-offs between iteration and recurrence and they range from simple to more complex. The paper also describes several iterative algorithms for computing the length of a Farey sequence based on these formulas. The algorithms are presented from the slowest to the fastest in order to explain the improvements in computational techniques from one version to another. The last algorithm in this progression runs in $$O(n^{2/3})$$

O
(

n

2
/
3

)

time and uses only $$O(\sqrt{n})$$

O
(

n

)

memory, which makes it the most efficient algorithm for computing $$|F_n|$$

|

F
n

|

described to date. With this algorithm we were able to compute the length of the Farey sequence of order $$10^{18}$$

10
18

.
Model-based estimation of transmissibility and reinfection of SARS-CoV-2 P.1 variant
Authors: Coutinho Renato Mendes , Marquitti Flavia Maria Darcie , Ferreira Leonardo Souto , Borges Marcelo Eduardo , da Silva Rafael Lopes Paixão , Canton Otavio , Portella Tatiana P. , Poloni Silas , Franco Caroline , Plucinski Mateusz M. , Lessa Fernanda C. , da Silva Antônio Augusto Moura , Kraenkel Roberto Andre , de Sousa Mascena Veras Maria Amélia , Prado Paulo Inácio 
Published: November 2021

AbstractBackgroundThe SARS-CoV-2 variant of concern (VOC) P.1 (Gamma variant) emerged in the Amazonas State, Brazil, in November 2020. The epidemiological consequences of its mutations have not been widely studied, despite detection of P.1 in 36 countries, with local transmission in at least 5 countries. A range of mutations are seen in P.1, ten of them in the spike protein. It shares mutations with VOCs previously detected in the United Kingdom (B.1.1.7, Alpha variant) and South Africa (B.1.351, Beta variant).MethodsWe estimated the transmissibility and reinfection of P.1 using a model-based approach, fitting data from the national health surveillance of hospitalized individuals and frequency of the P.1 variant in Manaus from December-2020 to February-2021.ResultsHere we estimate that the new variant is about 2.6 times more transmissible (95% Confidence Interval: 2.4–2.8) than previous circulating variant(s). Manaus already had a high prevalence of individuals previously affected by the SARS-CoV-2 virus and our fitted model attributed 28% of Manaus cases in the period to reinfections by P.1, confirming the importance of reinfection by this variant. This value is in line with estimates from blood donors samples in Manaus city.ConclusionsOur estimates rank P.1 as one of the most transmissible among the SARS-CoV-2 VOCs currently identified, and potentially as transmissible as the posteriorly detected VOC B.1.617.2 (Delta variant), posing a serious threat and requiring measures to control its global spread.
The trans/cis ratio of formic (HCOOH) and thioformic (HC(O)SH) acids in the interstellar medium
Authors: García de la Concepción J. , Colzi L. , Jiménez-Serra I. , Molpeceres G. , Corchado J. C. , Rivilla V. M. , Martín-Pintado J. , Beltrán M. T. , Mininni C. 
Published: November 2021

Context. Observations of the different isomers of molecules in the interstellar medium (ISM) have revealed that both low- and high-energy isomers can be present in space despite the low temperature conditions. It has been shown that the presence of these isomers may be due to tunneling effects.
Aims. We carried out a theoretical study of the cis–trans isomerization reactions of two astrophysically relevant acids, formic acid (HCOOH) and thioformic acid (HC(O)SH), where the latter has recently been discovered in space. We also searched for these molecules towards the hot core G31.41+0.31 to compare their abundances with the expected theoretical isomerization results.
Methods. We employed high-level ab initio calculations to study the reaction rate constants of the isomerization reactions. We used the canonical variational transition state theory with the multidimensional small curvature tunneling approximation in the temperature range of 10–400 K. Moreover, we used the spectrum obtained from the ALMA 3mm spectral survey GUAPOS (GUAPOS: G31 Unbiased ALMA sPectral Observational Survey), with a spectral resolution of ~0.488 MHz and an angular resolution of 1.′′2×1.′′2 (~4500 au), to derive column densities of HCOOH and HC(O)SH towards G31.41+0.31.
Results. Our results demonstrate that these isomerizations are viable in the conditions of the ISM due to ground-state tunneling effects, which allow the system to reach the thermodynamic equilibrium at moderately low temperatures. At very low temperatures (Tkin ~ 10 K), the reaction rate constants for the cis-to-trans isomerizations are very small, which implies that the cis isomers should not be formed under cold ISM conditions. This is in disagreement with observations of the cis/trans isomers of HCOOH in cold cores where the cis isomer is found to be ~5–6% the trans isomer. At high temperatures (~150–300 K), our theoretical data not only match the observed behavior of the trans/cis abundance ratios for HCOOH (the cis form is undetected), but they support our tentative detection of the trans and – for the first time in the insterstellar medium – the cis isomer of HC(O)SH towards the hot molecular core G31.41+0.31 (with a measured trans/cis abundance ratio of ~3.7).
Conclusions. While the trans/cis ratio for HC(O)SH in the ISM depends on the relative stability of the isomers, the trans/cis ratio for HCOOH cannot be explained by isomerization, and is determined by other competitive chemical processes.