bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Evolution of Mantle Plumes in East Africa
Authors: Chang Sung‐Joon , Kendall Elodie , Davaille Anne , Ferreira Ana M. G. 
Published: November 2020

AbstractGlobal tomography models show a large low‐velocity anomaly extending from the core‐mantle boundary (CMB) beneath South Africa to the upper mantle in East Africa. Although it is believed that this anomaly is linked to mantle upwellings that control key surface features of the African continent, its origin and evolution are still debated. Here we assemble geochemical and seismological constraints along with information from new seismic analyses and geodynamic laboratory experiments to propose that presently there are at least two different plume heads beneath Afar and Kenya that originated at the CMB. A third plume between Kenya and Afar may have caused the Ethiopia‐Yemen traps 30 Ma, now merging with the Afar plume. We infer that the Afar plume is presently detached from the CMB probably because of an interaction with the subducted Tethyan slab and that it is likely a dying plume. This may imply that rifts along the Main Ethiopian Rift would fail by the loss of thermal sources, which consequently hampers continental breakup.
Molybdenum and Boron Isotopic Compositions of Porphyry Cu Mineralization‐Related Adakitic Rocks in Central‐Eastern China: New Insights Into their Petrogenesis and Crust‐Mantle Interaction
Authors: Fan Jing‐Jing , Wang Qiang , Li Jie , Wei Gang‐Jian , Wyman Derek , Zhao Zhen‐Hua , Liu Ying , Ma Jin‐Long , Zhang Le , Wang Zi‐Long 
Published: November 2020

AbstractThe voluminous Late Mesozoic porphyry ore‐related adakitic magmatism in central‐eastern China is crucial to understand the deep geodynamic process of the region and controls on porphyry deposit formation globally. Here, we present a novel study of whole‐rock Mo‐B isotopes on the mineralization‐related adakitic rocks from the Dexing (located in the interior of South China and associated with giant porphyry Cu deposits), and Middle‐Lower Yangtze River (MLYR) (host to one of the largest porphyry Cu‐Au deposit belts) areas in central‐eastern China. The Dexing adakitic rocks have δ98/95Mo ranging from −0.31‰ to −0.01‰ and δ11B from −17.65‰ to −11.49‰. The adakitic rocks from the MLYR area have δ98/95Mo values of −0.5‰ to 0.2‰ and δ11B values of −14.48‰ to −9.53‰. The δ98/95Mo values of both the Dexing and MLYR samples negatively correlate with the La/Yb and La/Sm ratios. Together with the high Mg#, Cr, and Ni contents, these results indicate a process of melt‐mantle interaction resulting in hybridization of initial adakitic melts with low δ98/95Mo and mantle‐derived melts/components with high δ98/95Mo. These adakitic rocks have distinct Mo isotope systematics compared with those of oceanic slab‐derived adakites and MORB‐type eclogites. Their relatively low δ11B values and the lack of correlation between δ11B and B contents support a mafic lower crust source for the initial adakitic melts. We thus suggest that these adakitic rocks were generated by partial melting of delaminated lower crust followed by interaction with the deep mantle, and that melt‐mantle interaction may facilitate Cu‐Mo‐Au mineralization.
Subgroup level differences of physiological activities in marine Lokiarchaeota
Authors: Yin Xiuran , Cai Mingwei , Liu Yang , Zhou Guowei , Richter-Heitmann Tim , Aromokeye David A , Kulkarni Ajinkya C , Nimzyk Rolf , Cullhed Henrik , Zhou Zhichao , Pan Jie , Yang Yuchun , Gu Ji-Dong , Elvert Marcus , Li Meng , Friedrich Michael W 
Published: November 2020

Abstract
Asgard is a recently discovered archaeal superphylum, closely linked to the emergence of eukaryotes. Among Asgard archaea, Lokiarchaeota are abundant in marine sediments, but their in situ activities are largely unknown except for Candidatus ‘Prometheoarchaeum syntrophicum’. Here, we tracked the activity of Lokiarchaeota in incubations with Helgoland mud area sediments (North Sea) by stable isotope probing (SIP) with organic polymers, 13C-labelled inorganic carbon, fermentation intermediates and proteins. Within the active archaea, we detected members of the Lokiarchaeota class Loki-3, which appeared to mixotrophically participate in the degradation of lignin and humic acids while assimilating CO2, or heterotrophically used lactate. In contrast, members of the Lokiarchaeota class Loki-2 utilized protein and inorganic carbon, and degraded bacterial biomass formed in incubations. Metagenomic analysis revealed pathways for lactate degradation, and involvement in aromatic compound degradation in Loki-3, while the less globally distributed Loki-2 instead rely on protein degradation. We conclude that Lokiarchaeotal subgroups vary in their metabolic capabilities despite overlaps in their genomic equipment, and suggest that these subgroups occupy different ecologic niches in marine sediments.
Coexistence of perseveration and apathy in the TDP-43Q331K knock-in mouse model of ALS–FTD
Authors: Kim Eosu , White Matthew A. , Phillips Benjamin U. , Lopez-Cruz Laura , Kim Hyunjeong , Heath Christopher J. , Lee Jong Eun , Saksida Lisa M. , Sreedharan Jemeen , Bussey Timothy J. 
Published: November 2020

AbstractPerseveration and apathy are two of the most common behavioural and psychological symptoms of dementia (BPSDs) in amyotrophic lateral sclerosis–frontotemporal dementia (ALS–FTD). Availability of a validated and behaviourally characterised animal model is crucial for translational research into BPSD in the FTD context. We behaviourally evaluated the male TDP-43Q331K mouse, an ALS–FTD model with a human-equivalent mutation (TDP-43Q331K) knocked into the endogenous Tardbp gene. We utilised a panel of behavioural tasks delivered using the rodent touchscreen apparatus, including progressive ratio (PR), extinction and visual discrimination/reversal learning (VDR) assays to examine motivation, response inhibition and cognitive flexibility, respectively. Relative to WT littermates, TDP-43Q331K mice exhibited increased responding under a PR schedule. While elevated PR responding is typically an indication of increased motivation for reward, a trial-by-trial response rate analysis revealed that TDP-43Q331K mice exhibited decreased maximal response rate and slower response decay rate, suggestive of reduced motivation and a perseverative behavioural phenotype, respectively. In the extinction assay, TDP-43Q331K mice displayed increased omissions during the early phase of each session, consistent with a deficit in activational motivation. Finally, the VDR task revealed cognitive inflexibility, manifesting as stimulus-bound perseveration. Together, our data indicate that male TDP-43Q331K mice exhibit a perseverative phenotype with some evidence of apathy-like behaviour, similar to BPSDs observed in human ALS–FTD patients. The TDP-43Q331K knock-in mouse therefore has features that recommend it as a useful platform to facilitate translational research into behavioural symptoms in the context of ALS–FTD.
VIS832, a novel CD138-targeting monoclonal antibody, potently induces killing of human multiple myeloma and further synergizes with IMiDs or bortezomib in vitro and in vivo
Authors: Yu Tengteng , Chaganty Bharat , Lin Liang , Xing Lijie , Ramakrishnan Boopathy , Wen Kenneth , Hsieh Phillip A. , Wollacott Andrew , Viswanathan Karthik , Adari Hedy , Cho Shih-Feng , Li Yuyin , Chen Hailin , Yang Wenjuan , Xu Yan , An Gang , Qiu Lugui , Munshi Nikhil , Babcock Gregory , Shriver Zachary , Myette James R. , Anderson Kenneth C. , Tai Yu-Tzu 
Published: November 2020

AbstractTherapeutically targeting CD138, a define multiple myeloma (MM) antigen, is not yet approved for patients. We here developed and determined the preclinical efficacy of VIS832, a novel therapeutic monoclonal antibody (MoAb) with differentiated CD138 target binding to BB4 that is anti-CD138 MoAb scaffold for indatuximab ravtansine (BT062). VIS832 demonstrated enhanced CD138-binding avidity and significantly improved potency to kill MM cell lines and autologous patient MM cells regardless of resistance to current standard-of-care therapies, via robust antibody-dependent cellular cytotoxicity and phagocytosis mediated by NK and macrophage effector cells, respectively. Specifically, CD38-targeting daratumumab-resistant MM cells were highly susceptible to VIS832 which, unlike daratumumab, spares NK cells. Superior maximal cytolysis of VIS832 vs. daratumumab corresponded to higher CD138 vs. CD38 levels in MM cells. Furthermore, VIS832 acted synergistically with lenalidomide or bortezomib to deplete MM cells. Importantly, VIS832 at a sub-optimal dose inhibited disseminated MM1S tumors in vivo as monotherapy (P < 0.0001), and rapidly eradicated myeloma burden in all mice concomitantly receiving bortezomib, with 100% host survival. Taken together, these data strongly support clinical development of VIS832, alone and in combination, for the therapeutic treatment of MM in relapsed and refractory patients while pointing to its potential therapeutic use earlier in disease intervention.
An ambruticin-sensing complex modulates Myxococcus xanthus development and mediates myxobacterial interspecies communication
Authors: Marcos-Torres Francisco Javier , Volz Carsten , Müller Rolf 
Published: November 2020

AbstractStarvation induces cell aggregation in the soil bacterium Myxococcus xanthus, followed by formation of fruiting bodies packed with myxospores. Sporulation in the absence of fruiting bodies can be artificially induced by high concentrations of glycerol through unclear mechanisms. Here, we show that a compound (ambruticin VS-3) produced by a different myxobacterium, Sorangium cellulosum, affects the development of M. xanthus in a similar manner. Both glycerol (at millimolar levels) and ambruticin VS-3 (at nanomolar concentrations) inhibit M. xanthus fruiting body formation under starvation, and induce sporulation in the presence of nutrients. The response is mediated in M. xanthus by three hybrid histidine kinases (AskA, AskB, AskC) that form complexes interacting with two major developmental regulators (MrpC, FruA). In addition, AskB binds directly to the mrpC promoter in vitro. Thus, our work indicates that the AskABC-dependent regulatory pathway mediates the responses to ambruticin VS-3 and glycerol. We hypothesize that production of ambruticin VS-3 may allow S. sorangium to outcompete M. xanthus under both starvation and growth conditions in soil.
Sigma-1 receptor chaperones rescue nucleocytoplasmic transport deficit seen in cellular and Drosophila ALS/FTD models
Authors: Lee Pin-Tse , Liévens Jean-Charles , Wang Shao-Ming , Chuang Jian-Ying , Khalil Bilal , Wu Hsiang-en , Chang Wen-Chang , Maurice Tangui , Su Tsung-Ping 
Published: November 2020

ABSTRACTIn a subgroup of patients with amyotrophic lateral sclerosis (ALS)/Frontotemporal dementia (FTD), the (G4C2)-RNA repeat expansion from C9orf72 chromosome binds to the Ran-activating protein (RanGAP) at the nuclear pore, resulting in nucleocytoplasmic transport deficit and accumulation of Ran in the cytosol. Here, we found that the sigma-1 receptor (Sig-1R), a molecular chaperone, reverses the pathological effects of (G4C2)-RNA repeats in cell lines and in Drosophila. The Sig-1R colocalizes with RanGAP and nuclear pore proteins (Nups) and stabilizes the latter. Interestingly, Sig-1Rs directly bind (G4C2)-RNA repeats. Overexpression of Sig-1Rs rescues, whereas the Sig-1R knockout exacerbates, the (G4C2)-RNA repeats-induced aberrant cytoplasmic accumulation of Ran. In Drosophila, Sig-1R (but not the Sig-1R-E102Q mutant) overexpression reverses eye necrosis, climbing deficit, and firing discharge caused by (G4C2)-RNA repeats. These results on a molecular chaperone at the nuclear pore suggest that Sig-1Rs may benefit patients with C9orf72 ALS/FTD by chaperoning the nuclear pore assembly and sponging away deleterious (G4C2)-RNA repeats.
Perturbed structural dynamics underlie inhibition and altered efflux of the multidrug resistance pump AcrB
Authors: Reading Eamonn , Ahdash Zainab , Fais Chiara , Ricci Vito , Wang-Kan Xuan , Grimsey Elizabeth , Stone Jack , Malloci Giuliano , Lau Andy M. , Findlay Heather , Konijnenberg Albert , Booth Paula J. , Ruggerone Paolo , Vargiu Attilio V. , Piddock Laura J. V. , Politis Argyris 
Published: November 2020

AbstractResistance–nodulation–division efflux pumps play a key role in inherent and evolved multidrug resistance in bacteria. AcrB, a prototypical member of this protein family, extrudes a wide range of antimicrobial agents out of bacteria. Although high-resolution structures exist for AcrB, its conformational fluctuations and their putative role in function are largely unknown. Here, we determine these structural dynamics in the presence of substrates using hydrogen/deuterium exchange mass spectrometry, complemented by molecular dynamics simulations, and bacterial susceptibility studies. We show that an efflux pump inhibitor potentiates antibiotic activity by restraining drug-binding pocket dynamics, rather than preventing antibiotic binding. We also reveal that a drug-binding pocket substitution discovered within a multidrug resistant clinical isolate modifies the plasticity of the transport pathway, which could explain its altered substrate efflux. Our results provide insight into the molecular mechanism of drug export and inhibition of a major multidrug efflux pump and the directive role of its dynamics.
Pan-cancer landscape of homologous recombination deficiency
Authors: Nguyen Luan , W. M. Martens John , Van Hoeck Arne , Cuppen Edwin 
Published: November 2020

AbstractHomologous recombination deficiency (HRD) results in impaired double strand break repair and is a frequent driver of tumorigenesis. Here, we develop a genome-wide mutational scar-based pan-cancer Classifier of HOmologous Recombination Deficiency (CHORD) that can discriminate BRCA1- and BRCA2-subtypes. Analysis of a metastatic (n = 3,504) and primary (n = 1,854) pan-cancer cohort reveals that HRD is most frequent in ovarian and breast cancer, followed by pancreatic and prostate cancer. We identify biallelic inactivation of BRCA1, BRCA2, RAD51C or PALB2 as the most common genetic cause of HRD, with RAD51C and PALB2 inactivation resulting in BRCA2-type HRD. We find that while the specific genetic cause of HRD is cancer type specific, biallelic inactivation is predominantly associated with loss-of-heterozygosity (LOH), with increased contribution of deep deletions in prostate cancer. Our results demonstrate the value of pan-cancer genomics-based HRD testing and its potential diagnostic value for patient stratification towards treatment with e.g. poly ADP-ribose polymerase inhibitors (PARPi).
Geopositioning time series from offshore platforms in the Adriatic Sea
Authors: Palano Mimmo , Pezzo Giuseppe , Serpelloni Enrico , Devoti Roberto , D’Agostino Nicola , Gandolfi Stefano , Sparacino Federica , Anderlini Letizia , Poluzzi Luca , Tavasci Luca , Macini Paolo , Pietrantonio Grazia , Riguzzi Federica , Antoncecchi Ilaria , Ciccone Francesco , Rossi Giada , Avallone Antonio , Selvaggi Giulio 
Published: November 2020

AbstractWe provide a dataset of 3D coordinate time series of 37 continuous GNSS stations installed for stability monitoring purposes on onshore and offshore industrial settlements along a NW-SE-oriented and ~100-km-wide belt encompassing the eastern Italian coast and the Adriatic Sea. The dataset results from the analysis performed by using different geodetic software (Bernese, GAMIT/GLOBK and GIPSY) and consists of six raw position time series solutions, referred to IGb08 and IGS14 reference frames. Time series analyses and comparisons evidence that the different solutions are consistent between them, despite the use of different software, models, strategy processing and frame realizations. We observe that the offshore stations are subject to significant seasonal oscillations probably due to seasonal environmental loads, seasonal temperature-induced platform deformation and hydrostatic pressure variations. Many stations are characterized by non-linear time series, suggesting a complex interplay between regional (long-term tectonic stress) and local sources of deformation (e.g. reservoirs depletion, sediment compaction). Computed raw time series, logs files, phasor diagrams and time series comparison plots are distributed via PANGAEA (https://www.pangaea.de).
Inhaled corticosteroids in COPD and the risk for coronary heart disease: a nationwide cohort study
Authors: Shin Jiyoung , Yoon Hee-Young , Lee Yu Min , Ha Eunhee , Lee Jin Hwa 
Published: November 2020

AbstractInhaled corticosteroids (ICS) might lower the risk of coronary heart disease (CHD) in patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess the association of ICS with the development of CHD in COPD patients by using data from the Korean Nationwide study. Patients who were newly diagnosed with COPD between 2004 and 2013 and who were not diagnosed with coronary heart disease before their diagnosis of COPD were included. Exposure of ICS was incorporated into multivariable Cox regression models using time-dependent methods. To accurately estimate ICS-exposure accumulation, a washout period of 2 years from 2002 to 2003 was applied. Among a total of 4,400 newly diagnosed COPD patients, 771 patients were diagnosed as CHD incident cases during a median follow-up of one year (interquartile range 0.1–2.9). The cumulative dose of ICS was associated with a reduced risk of CHD (adjusted hazard ratio [aHR], 0.68; 95% confidence interval [CI], 0.52–0.89). When the cumulative exposure dose of ICS was divided into quartiles, the aHR for CHD incidence was 0.70 (95% CI, 0.55–0.88) in the highest quartile ICS dose use. The effect of ICS on reducing CHD incidence was pronounced in adults over 55 years, men under 55 years, and former smokers. Our findings demonstrate the role of ICS for the prevention of CHD in COPD patients without a history of CHD. Further research is needed to determine whether a certain amount of ICS exposure in COPD patients is protective against CHD.
Investigating the impact of captivity and domestication on limb bone cortical morphology: an experimental approach using a wild boar model
Authors: Harbers Hugo , Zanolli Clement , Cazenave Marine , Theil Jean-Christophe , Ortiz Katia , Blanc Barbara , Locatelli Yann , Schafberg Renate , Lecompte Francois , Baly Isabelle , Laurens Flavie , Callou Cécile , Herrel Anthony , Puymerail Laurent , Cucchi Thomas 
Published: November 2020

AbstractThe lack of bone morphological markers associated with the human control of wild animals has prevented the documentation of incipient animal domestication in archaeology. Here, we assess whether direct environmental changes (i.e. mobility reduction) could immediately affect ontogenetic changes in long bone structure, providing a skeletal marker of early domestication. We relied on a wild boar experimental model, analysing 24 wild-born specimens raised in captivity from 6 months to 2 years old. The shaft cortical thickness of their humerus was measured using a 3D morphometric mapping approach and compared with 23 free-ranging wild boars and 22 pigs from different breeds, taking into account sex, mass and muscle force differences. In wild boars we found that captivity induced an increase in cortical bone volume and muscle force, and a topographic change of cortical thickness associated with muscular expression along a phenotypic trajectory that differed from the divergence induced by selective breeding. These results provide an experimental proof of concept that changes in locomotor behaviour and selective breeding might be inferred from long bones morphology in the fossil and archaeological record. These trends need to be explored in the archaeological record and further studies are required to explore the developmental changes behind these plastic responses.
Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency
Authors: Løchen Alessandra , Croucher Nicholas J. , Anderson Roy M. 
Published: November 2020

AbstractStreptococcus pneumoniae is a significant cause of otitis media, pneumonia, and meningitis. Only seven of the approximately 100 serotypes were initially included in the pneumococcal polysaccharide conjugate vaccine (PCV) in 2000 before it was expanded in subsequent years. Although the invasive pneumococcal disease (IPD) incidence due to vaccine serotypes (VT) has declined, partial replacement by non-vaccine serotypes (NVT) was observed following widespread vaccine uptake. We conducted a trend analysis assembling the available evidence for PCV impact on European, North American and Australian national IPD. Significant effectiveness against VT IPD in infants was observed, although the impact on national IPD incidence varied internationally due to serotype replacement. Currently, NVT serotypes 8, 9N, 15A and 23B are increasing in the countries assessed, although a variety of other NVTs are affecting each country and age group. Despite these common emerging serotypes, there has not been a dominant IPD serotype post-vaccination as there was pre-vaccination (serotype 14) or post-PCV7 (serotype 19A), suggesting that future vaccines with additional serotypes will be less effective at targeting and reducing IPD in global populations than previous PCVs. The rise of diverse NVTs in all settings’ top-ranked IPD-causing serotypes emphasizes the urgent need for surveillance data on serotype distribution and serotype-specific invasiveness post-vaccination to facilitate decision making concerning both expanding current vaccination programmes and increasing vaccine valency.
Mirror replication of sexual facial expressions increases the success of sexual contacts in bonobos
Authors: Palagi Elisabetta , Bertini Marta , Annicchiarico Giulia , Cordoni Giada 
Published: November 2020

AbstractRapid Facial Mimicry (RFM), one of the possible predictors of emotional contagion, is defined as the rapid, involuntary and automatic replication of a facial expression. Up to now, RFM has been demonstrated in nonhuman animals exclusively during play. Since in bonobos, as in humans, socio-sexuality is a powerful tool for assessing/strengthening inter-individual relationships, we investigated RFM in this domain. Bonobos displayedsilent bared-teeth(sbt, the most common facial expression during sexual contacts) more frequently after thedetectionof ansbtemitted by the trigger than in theno-detectioncondition. This is the first demonstration of the presence of RFM during sex. The occurrence of RFM was positively affected by the sex of the partners with female homo-sexual contacts being punctuated by a higher presence of RFM. At an immediate level, RFM increased the duration of homo- and hetero-sexual contacts. This finding suggests that RFM can increase individuals’ potential fitness benefits. By prolonging their sexual contacts, females can strengthen their social relationships thus increasing the probability to obtain priority over resources (RFM indirect fitness benefits). Via longer copulations, males can increase the probability to make females pregnant (RFM direct fitness benefits). In conclusion, in bonobos the access to the partner’s face during sexual contacts (face-to-face, proximate factor) and the role of socio-sexuality in increasing the individual direct and indirect fitness (ultimate factor) could have favoured the evolution of specific sexual facial expressions and their rapid mirror replication. Our findings on bonobos expand the role of RFM well beyond the animal play domain thus opening new scenarios for future comparative studies exploring the evolution of socio-sexuality in humans.