bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon Sequestration Related to Soil Physical and Chemical Properties in the High Arctic
Authors: Jílková Veronika , Devetter Miloslav , Bryndová Michala , Hájek Tomáš , Kotas Petr , Luláková Petra , Meador Travis , Navrátilová Dana , Saccone Patrick , Macek Petr
Published: August 2021

Arctic soils are an important reservoir of soil organic carbon (SOC) and their role in determining arctic ecosystem functioning in global carbon budgets requires closer attention. We investigated the coupling of soil properties and SOC stabilization mechanisms in high Arctic terrestrial habitats differing in vegetation cover and organic matter input. We focused on soil physical and chemical properties in glacier foreland, soil crust, dry tundra, wet tundra, and bird cliff meadow habitats on Svalbard (Norway). Concurrently, we performed physical fractionation to determine the amount of SOC stabilized by mineral associations or occlusion in macro and microaggregates. Initial stages of soil development (glacier foreland and soil crust habitats) exhibited characteristically high bulk density and pH, and low moisture and nutrient contents, whereas more developed soils (dry and wet tundra habitats) showed opposite trends. Contrastingly, bird cliff meadow showed low bulk density, intermediate moisture, and very high nutrient content. The amount of SOC stabilized by mineral associations and occlusion in aggregates generally increased with vegetation cover; hence, the more developed habitats supported higher contents of stabilized SOC. However, SOC was stabilized in aggregates even in initial stages of soil development. SOC content in most fractions correlated positively with contents of dissolved organic carbon and nitrogen, suggesting that both dissolved organic carbon and nitrogen might have provided some degree of SOC stabilization through increased formation of aggregates and suppression of microbial mineralization of soil organic matter, respectively. Our findings underscore the notion that models of SOC sequestration in the Arctic should account not only for total SOC content, but also SOC stabilization mechanisms, as represented by SOC content in respective soil fractions.
Performance of Singular Spectrum Analysis in Separating Seasonal and Fast Physiological Dynamics of Solar‐Induced Chlorophyll Fluorescence and PRI Optical Signals
Authors: Biriukova Khelvi , Pacheco‐Labrador Javier , Migliavacca Mirco , Mahecha Miguel D. , Gonzalez‐Cascon Rosario , Martín M. Pilar , Rossini Micol
Published: August 2021

High temporal resolution measurements of solar‐induced chlorophyll fluorescence (F) and the Photochemical Reflectance Index (PRI) encode vegetation functioning. However, these signals are modulated by time‐dependent processes. We tested the applicability of the Singular Spectrum Analysis (SSA) for disentangling fast components (physiology‐driven) and slow components (controlled by structural and biochemical properties) from PRI, far‐red F (F760), and far‐red apparent fluorescence yield (Fy∗760). The proof of concept was developed on spectral and flux time series simulated with the Soil Canopy Observation of Photochemistry and Energy fluxes (SCOPE) model. This allowed the evaluation of SSA decomposition against variables that are independent of physiology or are modified by it. Slow SSA‐decomposed components of PRI and Fy∗760 showed high correlations with the reference variables (R2 = 0.97 and 0.96, respectively). Fast SSA‐decomposed components of PRI and Fy∗760 were better related to the physiological reference variables than the original signals during periods when leaf area index (LAI) was above 1 m2 m−2. The method was also successfully applied to predict light‐use efficiency (LUE) from the fast SSA‐decomposed components of PRI (R2 = 0.70) and Fy∗760 (R2 = 0.68) when discarding data modeled with LAI < 1 m2 m−2 and short‐wave radiation Rin < 250 W m−2. The method was then tested on data acquired in a Mediterranean grassland. In this case, the fast SSA‐decomposed component of apparent LUE∗ showed a stronger correlation with the fast SSA‐decomposed component of Fy∗760 (R2 = 0.42) than with original Fy∗760 (R2 = 0.01). SSA‐based approach is a promising tool for decoupling physiological information from measurements acquired with automated proximal sensing systems.
Wavelet and Network Analysis of Magnetic Field Variation and Geomagnetically Induced Currents During Large Storms
Authors: Orr L. , Chapman S. C. , Beggan C. D.
Published: August 2021

During geomagnetic storms rapid magnetic variations cause large, sharp enhancements of the magnetic and geoelectric field at mid‐latitudes. These present a potential hazard to grounded technology such as high voltage transformers, pipelines and railway systems. Spatiotemporal quantification can provide insight into the magnitude and configuration of their potential hazard. We use the Haar wavelet transform to localize in time and frequency the storm‐time response in both European ground‐based magnetometer measurements and modeled geomagnetically induced currents (GICs) from the high voltage grid of Great Britain (GB). Wavelet cross‐correlation of the GIC in the grounded nodes is then used to build a time‐varying network of GIC flow around the GB grid during storms including the 2003 Halloween storm. We find a highly intermittent (few tens of minutes duration) long‐range coherent response that can span the entire physical grid at most intense times. The spatial pattern of response seen in the GIC flow network does not simply follow that of the amplitude of the rate of change of B field. Coherent response is excited across spatially extended clusters comprised of a subset of nodes that are highly connected to each other, with a tendency for east‐west linkages following that of the physical grid, simultaneous with the overhead presence of the auroral electrojet and the inducing component of the magnetic field. This can quantify the spatial and temporal location of increased hazard in specific regions during large storms by including effects of both the geophysical and engineering configuration of the high voltage grid.
Place fields of single spikes in hippocampus involve Kcnq3 channel-dependent entrainment of complex spike bursts
Authors: Gao Xiaojie , Bender Franziska , Soh Heun , Chen Changwan , Altafi Mahsa , Schütze Sebastian , Heidenreich Matthias , Gorbati Maria , Corbu Mihaela-Anca , Carus-Cadavieco Marta , Korotkova Tatiana , Tzingounis Anastasios V. , Jentsch Thomas J. , Ponomarenko Alexey
Published: August 2021

Hippocampal pyramidal cells encode an animal’s location by single action potentials and complex spike bursts. These elementary signals are believed to play distinct roles in memory consolidation. The timing of single spikes and bursts is determined by intrinsic excitability and theta oscillations (5–10 Hz). Yet contributions of these dynamics to place fields remain elusive due to the lack of methods for specific modification of burst discharge. In mice lacking Kcnq3-containing M-type K+ channels, we find that pyramidal cell bursts are less coordinated by the theta rhythm than in controls during spatial navigation, but not alert immobility. Less modulated bursts are followed by an intact post-burst pause of single spike firing, resulting in a temporal discoordination of network oscillatory and intrinsic excitability. Place fields of single spikes in one- and two-dimensional environments are smaller in the mutant. Optogenetic manipulations of upstream signals reveal that neither medial septal GABA-ergic nor cholinergic inputs alone, but rather their joint activity, is required for entrainment of bursts. Our results suggest that altered representations by bursts and single spikes may contribute to deficits underlying cognitive disabilities associated with KCNQ3-mutations in humans.
Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis
Authors: Bodineau Clément , Tomé Mercedes , Courtois Sarah , Costa Ana S. H. , Sciacovelli Marco , Rousseau Benoit , Richard Elodie , Vacher Pierre , Parejo-Pérez Carlos , Bessede Emilie , Varon Christine , Soubeyran Pierre , Frezza Christian , Murdoch Piedad del Socorro , Villar Victor H. , Durán Raúl V.
Published: August 2021

Glutamoptosis is the induction of apoptotic cell death as a consequence of the aberrant activation of glutaminolysis and mTORC1 signaling during nutritional imbalance in proliferating cells. The role of the bioenergetic sensor AMPK during glutamoptosis is not defined yet. Here, we show that AMPK reactivation blocks both the glutamine-dependent activation of mTORC1 and glutamoptosis in vitro and in vivo. We also show that glutamine is used for asparagine synthesis and the GABA shunt to produce ATP and to inhibit AMPK, independently of glutaminolysis. Overall, our results indicate that glutamine metabolism is connected with mTORC1 activation through two parallel pathways: an acute alpha-ketoglutarate-dependent pathway; and a secondary ATP/AMPK-dependent pathway. This dual metabolic connection between glutamine and mTORC1 must be considered for the future design of therapeutic strategies to prevent cell growth in diseases such as cancer.
Manipulating crystallization dynamics through chelating molecules for bright perovskite emitters
Authors: Zou Yatao , Teng Pengpeng , Xu Weidong , Zheng Guanhaojie , Lin Weihua , Yin Jun , Kobera Libor , Abbrent Sabina , Li Xiangchun , Steele Julian A. , Solano Eduardo , Roeffaers Maarten B. J. , Li Jun , Cai Lei , Kuang Chaoyang , Scheblykin Ivan G. , Brus Jiri , Zheng Kaibo , Yang Ying , Mohammed Omar F. , Bakr Osman M. , Pullerits Tönu , Bai Sai , Sun Baoquan , Gao Feng
Published: August 2021

Molecular additives are widely utilized to minimize non-radiative recombination in metal halide perovskite emitters due to their passivation effects from chemical bonds with ionic defects. However, a general and puzzling observation that can hardly be rationalized by passivation alone is that most of the molecular additives enabling high-efficiency perovskite light-emitting diodes (PeLEDs) are chelating (multidentate) molecules, while their respective monodentate counterparts receive limited attention. Here, we reveal the largely ignored yet critical role of the chelate effect on governing crystallization dynamics of perovskite emitters and mitigating trap-mediated non-radiative losses. Specifically, we discover that the chelate effect enhances lead-additive coordination affinity, enabling the formation of thermodynamically stable intermediate phases and inhibiting halide coordination-driven perovskite nucleation. The retarded perovskite nucleation and crystal growth are key to high crystal quality and thus efficient electroluminescence. Our work elucidates the full effects of molecular additives on PeLEDs by uncovering the chelate effect as an important feature within perovskite crystallization. As such, we open new prospects for the rationalized screening of highly effective molecular additives.
Chronological genome and single-cell transcriptome integration characterizes the evolutionary process of adult T cell leukemia-lymphoma
Authors: Yamagishi Makoto , Kubokawa Miyuki , Kuze Yuta , Suzuki Ayako , Yokomizo Akari , Kobayashi Seiichiro , Nakashima Makoto , Makiyama Junya , Iwanaga Masako , Fukuda Takahiro , Watanabe Toshiki , Suzuki Yutaka , Uchimaru Kaoru
Published: August 2021

Subclonal genetic heterogeneity and their diverse gene expression impose serious problems in understanding the behavior of cancers and contemplating therapeutic strategies. Here we develop and utilize a capture-based sequencing panel, which covers host hotspot genes and the full-length genome of human T-cell leukemia virus type-1 (HTLV-1), to investigate the clonal architecture of adult T-cell leukemia-lymphoma (ATL). For chronologically collected specimens from patients with ATL or pre-onset individuals, we integrate deep DNA sequencing and single-cell RNA sequencing to detect the somatic mutations and virus directly and characterize the transcriptional readouts in respective subclones. Characteristic genomic and transcriptomic patterns are associated with subclonal expansion and switches during the clinical timeline. Multistep mutations in the T-cell receptor (TCR), STAT3, and NOTCH pathways establish clone-specific transcriptomic abnormalities and further accelerate their proliferative potential to develop highly malignant clones, leading to disease onset and progression. Early detection and characterization of newly expanded subclones through the integrative analytical platform will be valuable for the development of an in-depth understanding of this disease.
Altered function and differentiation of age-associated B cells contribute to the female bias in lupus mice
Authors: Ricker Edd , Manni Michela , Flores-Castro Danny , Jenkins Daniel , Gupta Sanjay , Rivera-Correa Juan , Meng Wenzhao , Rosenfeld Aaron M. , Pannellini Tania , Bachu Mahesh , Chinenov Yurii , Sculco Peter K. , Jessberger Rolf , Prak Eline T. Luning , Pernis Alessandra B.
Published: August 2021

Differences in immune responses to viruses and autoimmune diseases such as systemic lupus erythematosus (SLE) can show sexual dimorphism. Age-associated B cells (ABC) are a population of CD11c+T-bet+ B cells critical for antiviral responses and autoimmune disorders. Absence of DEF6 and SWAP-70, two homologous guanine exchange factors, in double-knock-out (DKO) mice leads to a lupus-like syndrome in females marked by accumulation of ABCs. Here we demonstrate that DKO ABCs show sex-specific differences in cell number, upregulation of an ISG signature, and further differentiation. DKO ABCs undergo oligoclonal expansion and differentiate into both CD11c+ and CD11c− effector B cell populations with pathogenic and pro-inflammatory function as demonstrated by BCR sequencing and fate-mapping experiments. Tlr7 duplication in DKO males overrides the sex-bias and further augments the dissemination and pathogenicity of ABCs, resulting in severe pulmonary inflammation and early mortality. Thus, sexual dimorphism shapes the expansion, function and differentiation of ABCs that accompanies TLR7-driven immunopathogenesis.
Emerging symmetric strain response and weakening nematic fluctuations in strongly hole-doped iron-based superconductors
Authors: Wiecki P. , Frachet M. , Haghighirad A.-A. , Wolf T. , Meingast C. , Heid R. , Böhmer A. E.
Published: August 2021

Electronic nematicity is often found in unconventional superconductors, suggesting its relevance for electronic pairing. In the strongly hole-doped iron-based superconductors, the symmetry channel and strength of the nematic fluctuations, as well as the possible presence of long-range nematic order, remain controversial. Here, we address these questions using transport measurements under elastic strain. By decomposing the strain response into the appropriate symmetry channels, we demonstrate the emergence of a giant in-plane symmetric contribution, associated with the growth of both strong electronic correlations and the sensitivity of these correlations to strain. We find weakened remnants of the nematic fluctuations that are present at optimal doping, but no change in the symmetry channel of nematic fluctuations with hole doping. Furthermore, we find no indication of a nematic-ordered state in the AFe2As2 (A = K, Rb, Cs) superconductors. These results revise the current understanding of nematicity in hole-doped iron-based superconductors.
Predictive biomarkers for 5-fluorouracil and oxaliplatin-based chemotherapy in gastric cancers via profiling of patient-derived xenografts
Authors: Na Deukchae , Chae Jeesoo , Cho Sung-Yup , Kang Wonyoung , Lee Ahra , Min Seoyeon , Kang Jinjoo , Kim Min Jung , Choi Jaeyong , Lee Woochan , Shin Dongjin , Min Ahrum , Kim Yu-Jin , Lee Kyung-Hun , Kim Tae-Yong , Suh Yun-Suhk , Kong Seong-Ho , Lee Hyuk-Joon , Kim Woo-Ho , Park Hansoo , Im Seock-Ah , Yang Han-Kwang , Lee Charles , Kim Jong-Il
Published: August 2021

Gastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PDXs are defined as either responders or non-responders according to tumor volume change after treatment, the responsiveness of PDXs is significantly consistent with the respective clinical outcomes of the patients. An integrative genomic and transcriptomic analysis of PDXs reveals that pathways associated with cell-to-cell and cell-to-extracellular matrix interactions enriched among the non-responders in both cancer cells and the tumor microenvironment (TME). We develop a 30-gene prediction model to determine the responsiveness to 5-FU and oxaliplatin-based chemotherapy and confirm the significant poor survival outcomes among cases classified as non-responder-like in three independent GC cohorts. Our study may inform clinical decision-making when designing treatment strategies.
The molecular basis, genetic control and pleiotropic effects of local gene co-expression
Authors: Ribeiro Diogo M. , Rubinacci Simone , Ramisch Anna , Hofmeister Robin J. , Dermitzakis Emmanouil T. , Delaneau Olivier
Published: August 2021

Nearby genes are often expressed as a group. Yet, the prevalence, molecular mechanisms and genetic control of local gene co-expression are far from being understood. Here, by leveraging gene expression measurements across 49 human tissues and hundreds of individuals, we find that local gene co-expression occurs in 13% to 53% of genes per tissue. By integrating various molecular assays (e.g. ChIP-seq and Hi-C), we estimate the ability of several mechanisms, such as enhancer-gene interactions, in distinguishing gene pairs that are co-expressed from those that are not. Notably, we identify 32,636 expression quantitative trait loci (eQTLs) which associate with co-expressed gene pairs and often overlap enhancer regions. Due to affecting several genes, these eQTLs are more often associated with multiple human traits than other eQTLs. Our study paves the way to comprehend trait pleiotropy and functional interpretation of QTL and GWAS findings. All local gene co-expression identified here is available through a public database (https://glcoex.unil.ch/).
Sound trapping in an open resonator
Authors: Huang Lujun , Chiang Yan Kei , Huang Sibo , Shen Chen , Deng Fu , Cheng Yi , Jia Bin , Li Yong , Powell David A. , Miroshnichenko Andrey E.
Published: August 2021

The ability of sound energy confinement with high-quality factor resonance is of vital importance for acoustic devices requiring high intensity and hypersensitivity in biological ultrasonics, enhanced collimated sound emission (i.e. sound laser) and high-resolution sensing. However, structures reported so far have been experimentally demonstrated with a limited quality factor of acoustic resonances, up to several tens in an open resonator. The emergence of bound states in the continuum makes it possible to realize high quality factor acoustic modes. Here, we report the theoretical design and experimental demonstration of acoustic bound states in the continuum supported by a single open resonator. We predicted that such an open acoustic resonator could simultaneously support three types of bound states in the continuum, including symmetry protected bound states in the continuum, Friedrich-Wintgen bound states in the continuum induced by mode interference, as well as a new type-mirror symmetry induced bound states in the continuum. We also experimentally demonstrated their existence with quality factor up to one order of magnitude greater than the highest quality factor reported in an open resonator.
Tracking the introduction and spread of SARS-CoV-2 in coastal Kenya
Authors: Githinji George , de Laurent Zaydah R. , Mohammed Khadija Said , Omuoyo Donwilliams O. , Macharia Peter M. , Morobe John M. , Otieno Edward , Kinyanjui Samson M. , Agweyu Ambrose , Maitha Eric , Kitole Ben , Suleiman Thani , Mwakinangu Mohamed , Nyambu John , Otieno John , Salim Barke , Kasera Kadondi , Kiiru John , Aman Rashid , Barasa Edwine , Warimwe George , Bejon Philip , Tsofa Benjamin , Ochola-Oyier Lynette Isabella , Nokes D. James , Agoti Charles N.
Published: August 2021

Genomic surveillance of SARS-CoV-2 is important for understanding both the evolution and the patterns of local and global transmission. Here, we generated 311 SARS-CoV-2 genomes from samples collected in coastal Kenya between 17th March and 31st July 2020. We estimated multiple independent SARS-CoV-2 introductions into the region were primarily of European origin, although introductions could have come through neighbouring countries. Lineage B.1 accounted for 74% of sequenced cases. Lineages A, B and B.4 were detected in screened individuals at the Kenya-Tanzania border or returning travellers. Though multiple lineages were introduced into coastal Kenya following the initial confirmed case, none showed extensive local expansion other than lineage B.1. International points of entry were important conduits of SARS-CoV-2 importations into coastal Kenya and early public health responses prevented established transmission of some lineages. Undetected introductions through points of entry including imports from elsewhere in the country gave rise to the local epidemic at the Kenyan coast.
Theta-phase dependent neuronal coding during sequence learning in human single neurons
Authors: Reddy Leila , Self Matthew W. , Zoefel Benedikt , Poncet Marlène , Possel Jessy K. , Peters Judith C. , Baayen Johannes C. , Idema Sander , VanRullen Rufin , Roelfsema Pieter R.
Published: August 2021

The ability to maintain a sequence of items in memory is a fundamental cognitive function. In the rodent hippocampus, the representation of sequentially organized spatial locations is reflected by the phase of action potentials relative to the theta oscillation (phase precession). We investigated whether the timing of neuronal activity relative to the theta brain oscillation also reflects sequence order in the medial temporal lobe of humans. We used a task in which human participants learned a fixed sequence of pictures and recorded single neuron and local field potential activity with implanted electrodes. We report that spikes for three consecutive items in the sequence (the preferred stimulus for each cell, as well as the stimuli immediately preceding and following it) were phase-locked at distinct phases of the theta oscillation. Consistent with phase precession, spikes were fired at progressively earlier phases as the sequence advanced. These findings generalize previous findings in the rodent hippocampus to the human temporal lobe and suggest that encoding stimulus information at distinct oscillatory phases may play a role in maintaining sequential order in memory.
Small tandem DNA duplications result from CST-guided Pol α-primase action at DNA break termini
Authors: Schimmel Joost , Muñoz-Subirana Núria , Kool Hanneke , van Schendel Robin , Tijsterman Marcel
Published: August 2021

Small tandem duplications of DNA occur frequently in the human genome and are implicated in the aetiology of certain human cancers. Recent studies have suggested that DNA double-strand breaks are causal to this mutational class, but the underlying mechanism remains elusive. Here, we identify a crucial role for DNA polymerase α (Pol α)-primase in tandem duplication formation at breaks having complementary 3′ ssDNA protrusions. By including so-called primase deserts in CRISPR/Cas9-induced DNA break configurations, we reveal that fill-in synthesis preferentially starts at the 3′ tip, and find this activity to be dependent on 53BP1, and the CTC1-STN1-TEN1 (CST) and Shieldin complexes. This axis generates near-blunt ends specifically at DNA breaks with 3′ overhangs, which are subsequently repaired by non-homologous end-joining. Our study provides a mechanistic explanation for a mutational signature abundantly observed in the genomes of species and cancer cells.
Exciton-driven antiferromagnetic metal in a correlated van der Waals insulator
Authors: Belvin Carina A. , Baldini Edoardo , Ozel Ilkem Ozge , Mao Dan , Po Hoi Chun , Allington Clifford J. , Son Suhan , Kim Beom Hyun , Kim Jonghyeon , Hwang Inho , Kim Jae Hoon , Park Je-Geun , Senthil T. , Gedik Nuh
Published: August 2021

Collective excitations of bound electron-hole pairs—known as excitons—are ubiquitous in condensed matter, emerging in systems as diverse as band semiconductors, molecular crystals, and proteins. Recently, their existence in strongly correlated electron materials has attracted increasing interest due to the excitons’ unique coupling to spin and orbital degrees of freedom. The non-equilibrium driving of such dressed quasiparticles offers a promising platform for realizing unconventional many-body phenomena and phases beyond thermodynamic equilibrium. Here, we achieve this in the van der Waals correlated insulator NiPS3 by photoexciting its newly discovered spin–orbit-entangled excitons that arise from Zhang-Rice states. By monitoring the time evolution of the terahertz conductivity, we observe the coexistence of itinerant carriers produced by exciton dissociation and a long-wavelength antiferromagnetic magnon that coherently precesses in time. These results demonstrate the emergence of a transient metallic state that preserves long-range antiferromagnetism, a phase that cannot be reached by simply tuning the temperature. More broadly, our findings open an avenue toward the exciton-mediated optical manipulation of magnetism.
Myocardial fibrosis reversion via rhACE2-electrospun fibrous patch for ventricular remodeling prevention
Authors: Qiu Zeping , Zhao Jingwen , Huang Fanyi , Bao Luhan , Chen Yanjia , Yang Ke , Cui Wenguo , Jin Wei
Published: August 2021

Myocardial fibrosis and ventricular remodeling were the key pathology factors causing undesirable consequence after myocardial infarction. However, an efficient therapeutic method remains unclear, partly due to difficulty in continuously preventing neurohormonal overactivation and potential disadvantages of cell therapy for clinical practice. In this study, a rhACE2-electrospun fibrous patch with sustained releasing of rhACE2 to shape an induction transformation niche in situ was introduced, through micro-sol electrospinning technologies. A durable releasing pattern of rhACE2 encapsulated in hyaluronic acid (HA)—poly(L-lactic acid) (PLLA) core-shell structure was observed. By multiple in vitro studies, the rhACE2 patch demonstrated effectiveness in reducing cardiomyocytes apoptosis under hypoxia stress and inhibiting cardiac fibroblasts proliferation, which gave evidence for its in vivo efficacy. For striking mice myocardial infarction experiments, a successful prevention of adverse ventricular remodeling has been demonstrated, reflecting by improved ejection fraction, normal ventricle structure and less fibrosis. The rhACE2 patch niche showed clear superiority in long term function and structure preservation after ischemia compared with intramyocardial injection. Thus, the micro-sol electrospun rhACE2 fibrous patch niche was proved to be efficient, cost-effective and easy-to-use in preventing ventricular adverse remodeling.
Identification of prognostic biomarkers related to the tumor microenvironment in thyroid carcinoma
Authors: Du Jun-wei , Li Guo-quan , Li Yang-sen , Qiu Xin-guang
Published: August 2021

Thyroid Carcinoma (THCA) is the most common endocrine tumor that is mainly treated using surgery and radiotherapy. In addition, immunotherapy is a recently developed treatment option that has played an essential role in the management of several types of tumors. However, few reports exist on the use of immunotherapy to treat THCA. The study downloaded the miRNA, mRNA and lncRNA data for THCA patients from the TCGA database (https://portal.gdc.cancer.gov/). Thereafter, the tumor samples were divided into cold and hot tumors, based on the immune score of the tumor microenvironment. Moreover, the differentially expressed lncRNAs and miRNAs were obtained. Finally, the study jointly constructed a ceRNA network through differential analysis of the mRNA data for cold and hot tumors. The study first assessed the level of immune infiltration in the THCA tumor microenvironment then divided the samples into cold and hot tumors, based on the immune score. Additionally, a total of 568 up-regulated and 412 down-regulated DEGs were screened by analyzing the differences between hot and cold tumors. Thereafter, the study examined the differentially expressed genes for lncRNA and miRNA. The results revealed 629 differentially expressed genes related to lncRNA and 114 associated with miRNA. Finally, a ceRNA network of the differentially expressed genes was constructed. The results showed a five-miRNA hubnet, i.e., hsa-mir-204, hsa-mir-128, hsa-mir-214, hsa-mir-150 and hsa-mir-338. The present study identified the immune-related mRNA, lncRNA and miRNA in THCA then constructed a ceRNA network. These results are therefore important as they provide more insights on the immune mechanisms in THCA. The findings also provides additional information for possible THCA immunotherapy.
Uncertainty in experts’ judgments exposes the vulnerability of research reporting anecdotes on animals’ cognitive abilities
Authors: Sándor Krisztina , Könnyű Balázs , Miklósi Ádám
Published: August 2021

Expertise in science, particularly in animal behaviour, may provide people with the capacity to provide better judgments in contrast to lay people. Here we explore whether experts provide a more objective, accurate and coherent evaluation of a recently reported anecdote on Atlantic puffin (Fratercula arctica) “tool use” (recorded on video) which was published in a major scientific journal but was received with some scepticism. We relied on citizen science and developed a questionnaire to measure whether experts in ethology and ornithology and lay people agree or disagree on (1) the description of the actions that they observe (the bird takes a stick in its beak), (2) the possible goal of the action (nest-building or grooming) and (3) the intentional component of the action (the bird took the stick into its beak in order to scratch itself). We hypothesised that contrary to the lay people, experts are more critical evaluators that is they are more inclined to report alternative actions, like nest building, or are less likely to attributing goal-directedness to the action in the absence of evidence. In contrast, lay people may be more prone to anthropomorphise utilising a teleological and intentional stance. Alternatively, all three groups of subjects may rely on anthropomorphism at similar levels and prior expertise does not play a significant role. We found that no major differences among the evaluators. At the group levels, respondents were relatively uncertain with regard to the action of the bird seen on the video but they showed some individual consistency with regard to the description of the action. Thus, we conclude that paradoxically, with regard to the task our experts are typically not experts in the strict sense of the definition, and suggest that anecdotal reports should not be used to argue about mental processes.
Bioactive recombinant human oncostatin M for NMR-based screening in drug discovery
Authors: Mass Olga A. , Tuccinardi Joseph , Woodbury Luke , Wolf Cody L. , Grantham Bri , Holdaway Kelsey , Pu Xinzhu , King Matthew D. , Warner Don L. , Jorcyk Cheryl L. , Warner Lisa R.
Published: August 2021

Oncostatin M (OSM) is a pleiotropic, interleukin-6 family inflammatory cytokine that plays an important role in inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer progression and metastasis. Recently, elevated OSM levels have been found in the serum of COVID-19 patients in intensive care units. Multiple anti-OSM therapeutics have been investigated, but to date no OSM small molecule inhibitors are clinically available. To pursue a high-throughput screening and structure-based drug discovery strategy to design a small molecule inhibitor of OSM, milligram quantities of highly pure, bioactive OSM are required. Here, we developed a reliable protocol to produce highly pure unlabeled and isotope enriched OSM fromE. colifor biochemical and NMR studies. High yields (ca. 10 mg/L culture) were obtained in rich and minimal defined media cultures. Purified OSM was characterized by mass spectrometry and circular dichroism. The bioactivity was confirmed by induction of OSM/OSM receptor signaling through STAT3 phosphorylation in human breast cancer cells. Optimized buffer conditions yielded1H,15N HSQC NMR spectra with intense, well-dispersed peaks. Titration of15N OSM with a small molecule inhibitor showed chemical shift perturbations for several key residues with a binding affinity of 12.2 ± 3.9 μM. These results demonstrate the value of bioactive recombinant human OSM for NMR-based small molecule screening.
Robust and fast post-processing of single-shot spin qubit detection events with a neural network
Authors: Struck Tom , Lindner Javed , Hollmann Arne , Schauer Floyd , Schmidbauer Andreas , Bougeard Dominique , Schreiber Lars R.
Published: August 2021

Establishing low-error and fast detection methods for qubit readout is crucial for efficient quantum error correction. Here, we test neural networks to classify a collection of single-shot spin detection events, which are the readout signal of our qubit measurements. This readout signal contains a stochastic peak, for which a Bayesian inference filter including Gaussian noise is theoretically optimal. Hence, we benchmark our neural networks trained by various strategies versus this latter algorithm. Training of the network with 106 experimentally recorded single-shot readout traces does not improve the post-processing performance. A network trained by synthetically generated measurement traces performs similar in terms of the detection error and the post-processing speed compared to the Bayesian inference filter. This neural network turns out to be more robust to fluctuations in the signal offset, length and delay as well as in the signal-to-noise ratio. Notably, we find an increase of 7% in the visibility of the Rabi oscillation when we employ a network trained by synthetic readout traces combined with measured signal noise of our setup. Our contribution thus represents an example of the beneficial role which software and hardware implementation of neural networks may play in scalable spin qubit processor architectures.
The nervous system of the most complex lophophore provides new insights into the evolution of Brachiopoda
Authors: Temereva Elena N. , Kuzmina Tatyana V.
Published: August 2021

The lophophore is a tentacle organ unique to the lophophorates. Recent research has revealed that the organization of the nervous and muscular systems of the lophophore is similar in phoronids, brachiopods, and bryozoans. At the same time, the evolution of the lophophore in certain lophophorates is still being debated. Innervation of the adult lophophore has been studied by immunocytochemistry and confocal laser scanning microscopy for only two brachiopod species belonging to two subphyla: Linguliformea and Rhynchonelliformea. Species from both groups have the spirolophe, which is the most common type of the lophophore among brachiopods. In this study, we used transmission electron microscopy, immunocytochemistry, and confocal laser scanning microscopy to describe the innervation of the most complex lophophore (the plectolophe) of the rhynchonelliform speciesCoptothyris grayi. TheC. grayilophophore (the plectolophe) is innervated by three brachial nerves: the main, second accessory, and lower. Thus, the plectolophe lacks the accessory brachial nerve, which is typically present in other studied brachiopods. AllC. grayibrachial nerves contain two types of perikarya. Because the accessory nerve is absent, the cross nerves, which pass into the connective tissue, have a complex morphology: each nerve consists of two ascending and one descending branches. The outer and inner tentacles are innervated by several groups of neurite bundles: one frontal, two lateral, two abfrontal, and two latero-abfrontal (the latter is present in only the outer tentacles). Tentacle nerves originate from the second accessory and lower brachial nerves. The inner and outer tentacles are also innervated by numerous peritoneal neurites, which exhibit acetylated alpha-tubulin-like immunoreactivity. The nervous system of the lophophore ofC. grayimanifests several evolutionary trends. On the one hand, it has undergone simplification, i.e., the absence of the accessory brachial nerve, which is apparently correlated with a reduction in the complexity of the lophophore’s musculature. On the other hand,C. grayihas a prominent second accessory nerve, which contains large groups of frontal perikarya, and also has additional nerves extending from the both ganglia to the medial arm; these features are consistent with the complex morphology of theC.grayi plectolophe. In brachiopods, the evolution of the lophophore nervous system apparently involved two main modifications. The first modification was the appearance and further strengthening of the second accessory brachial nerve, which apparently arose because of the formation of a double row of tentacles instead of the single row of the brachiopod ancestor. The second modification was the partial or complete reduction of some brachial nerves, which was correlated with the reduced complexity of the lophophore musculature and the appearance of skeletal structures that support the lophophore.
Nanostructured versus flat compact electrode for triboelectric nanogenerators at high humidity
Authors: Karimi Masoume , Seddighi Sadegh , Mohammadpour Raheleh
Published: August 2021

The triboelectric nanogenerator (TENG) is a promising technology for mechanical energy harvesting. TENG has proven to be an excellent option for power generation but typically TENGs output power drops significantly in humid environments. In this work, the effect of electrode’s material on power output, considering smooth and nanostructured porous structures with various surface hydrophobicity, is investigated under various humidity conditions. A vertical contact-separation mode TENG is experimentally and numerically studied for four surface morphologies of Ti foil, TiO2 thin film, TiO2 nanoparticulated film, and TiO2 nanotubular electrodes. The results show that the TENG electrical output in the flat structures such as Ti foil and TiO2 thin film at 50% RH is reduced to 50% of its initial state, while in the nanoporous structures such as nanoparticle and nanotube arrays, this is observed at RH above 95%. The results show that the use of porous nanostructures in TENG due to their high surface-to-volume, and that the process of water adsorption on the pore leads to better performance than the flat surface in humid environments. Based on our study, employing nanoporous layers is vital for nanogenerators either for power generation or active sensor applications at high humidity conditions.
Small pigmented eukaryote assemblages of the western tropical North Atlantic around the Amazon River plume during spring discharge
Authors: Charvet Sophie , Kim Eunsoo , Subramaniam Ajit , Montoya Joseph , Duhamel Solange
Published: August 2021

Small pigmented eukaryotes (⩽ 5 µm) are an important, but overlooked component of global marine phytoplankton. The Amazon River plume delivers nutrients into the oligotrophic western tropical North Atlantic, shades the deeper waters, and drives the structure of microphytoplankton (> 20 µm) communities. For small pigmented eukaryotes, however, diversity and distribution in the region remain unknown, despite their significant contribution to open ocean primary production and other biogeochemical processes. To investigate how habitats created by the Amazon river plume shape small pigmented eukaryote communities, we used high-throughput sequencing of the 18S ribosomal RNA genes from up to five distinct small pigmented eukaryote cell populations, identified and sorted by flow cytometry. Small pigmented eukaryotes dominated small phytoplankton biomass across all habitat types, but the population abundances varied among stations resulting in a random distribution. Small pigmented eukaryote communities were consistently dominated by Chloropicophyceae (0.8–2 µm) and Bacillariophyceae (0.8–3.5 µm), accompanied by MOCH-5 at the surface or by Dinophyceae at the chlorophyll maximum. Taxonomic composition only displayed differences in the old plume core and at one of the plume margin stations. Such results reflect the dynamic interactions of the plume and offshore oceanic waters and suggest that the resident small pigmented eukaryote diversity was not strongly affected by habitat types at this time of the year.
Hyperspectral image processing for the identification and quantification of lentiviral particles in fluid samples
Authors: Gomez-Gonzalez Emilio , Fernandez-Muñoz Beatriz , Barriga-Rivera Alejandro , Navas-Garcia Jose Manuel , Fernandez-Lizaranzu Isabel , Munoz-Gonzalez Francisco Javier , Parrilla-Giraldez Ruben , Requena-Lancharro Desiree , Guerrero-Claro Manuel , Gil-Gamboa Pedro , Rosell-Valle Cristina , Gomez-Gonzalez Carmen , Mayorga-Buiza Maria Jose , Martin-Lopez Maria , Muñoz Olga , Martin Juan Carlos Gomez , Lopez Maria Isabel Relimpio , Aceituno-Castro Jesus , Perales-Esteve Manuel A. , Puppo-Moreno Antonio , Cozar Francisco Jose Garcia , Olvera-Collantes Lucia , de los Santos-Trigo Silvia , Gomez Emilia , Pernaute Rosario Sanchez , Padillo-Ruiz Javier , Marquez-Rivas Javier
Published: August 2021

Optical spectroscopic techniques have been commonly used to detect the presence of biofilm-forming pathogens (bacteria and fungi) in the agro-food industry. Recently, near-infrared (NIR) spectroscopy revealed that it is also possible to detect the presence of viruses in animal and vegetal tissues. Here we report a platform based on visible and NIR (VNIR) hyperspectral imaging for non-contact, reagent free detection and quantification of laboratory-engineered viral particles in fluid samples (liquid droplets and dry residue) using both partial least square-discriminant analysis and artificial feed-forward neural networks. The detection was successfully achieved in preparations of phosphate buffered solution and artificial saliva, with an equivalent pixel volume of 4 nL and lowest concentration of 800 TU·$$\upmu$$
μ
L−1. This method constitutes an innovative approach that could be potentially used at point of care for rapid mass screening of viral infectious diseases and monitoring of the SARS-CoV-2 pandemic.
Multicentric real world evidence with palbociclib in hormone positive HER2 negative metastatic breast cancer in Indian population
Authors: Agrawal Chaturbhuj , Goyal Pankaj , Agarwal Amit , Tripathi Rupal , Dodagoudar Chandragouda , Baghmar Saphalta , Sharma Archana , Batra Ullas , Talwar Vineet , Goyal Sumit , Kumar Rajeev , Doval Dinesh Chandra
Published: August 2021

The combination of cyclin dependent kinase 4/6 inhibitors with endocrine therapy is the standard therapy in hormone receptor positive HER-2 negative metastatic breast cancer (HR+/HER2− MBC). Several randomized trials have shown the benefits of this combination, however, real world evidence in the Indian patients is warranted. The present study reports the largest real world multicentric data from Indian population on the use of Palbociclib in HR+/HER2− MBC. A multicentric study on the HR+/HER2− MBC patients who received palbociclib with hormonal agent (Aromatase inhibitors/Fulvestrant) between February 2017 and May 2020 was conducted. Clinical and demographic information and survival data was retrieved from the Hospital medical records. Among a total of 188 patients, 57% patients were premenopausal and 17% patients had bone only disease. Altogether, 115 (61%) patients received palbociclib with Aromatase inhibitors in the first line whereas 73 (39%) patients received it in the second line with Fulvestrant. The median follow up period with advanced disease was 13 months. The median progression free survival in the first line and second line was 20.2 months and 12 months, respectively (p-value < 0.0001). The objective response rate was 80% and 47.9% in first and second lines, respectively. Dose interruptions/ discontinuation were done in 14.9% and 2.7% patients in the first and second lines, respectively. In terms of toxicity, 10% patients had grade 3–4 adverse events. The present real world data of the use of palbociclib in Indian population suggests similar effectiveness to previously published real world evidences and has been adapted as the standard of care in the first and second line treatment of HR+/HER2− MBC.
Significance of serum palmitoleic acid levels in inflammatory bowel disease
Authors: Akazawa Yuko , Morisaki Tomohito , Fukuda Hiroko , Norimatsu Kiyuu , Shiota Junya , Hashiguchi Keiichi , Tabuchi Maiko , Kitayama Moto , Matsushima Kayoko , Yamaguchi Naoyuki , Kondo Hisayoshi , Fujita Fumihiko , Takeshita Hiroaki , Nakao Kazuhiko , Takeshima Fuminao
Published: August 2021

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic intestinal diseases of unknown etiology that present with variable disease extents and outcomes. The use of biomarkers for the diagnosis and management of IBDs is considered beneficial. Palmitoleic acid (PO) is an adipose tissue-derived mono-unsaturated free fatty acid that potentially serves as a lipokine in metabolic and inflammatory diseases. The aim of this study was to investigate the significance of PO levels in the serum of patients with UC and CD. The study included patients with UC (n = 22), patients with CD (n = 35), and controls (n = 22). The levels of serum PO were analyzed using gas chromatography. The association of serum PO levels with the clinical features and disease outcomes in IBD was examined. Serum PO levels were significantly higher in patients with CD than in controls, whereas no difference in these levels was observed between patients with UC and controls. Serum PO levels were significantly associated with the CD activity index. Additionally, high serum PO levels were associated with an increased risk of surgical intervention requirement during follow-up. In a pilot study with a few patients, high PO levels were observed in the mesenteric tissue in the active disease site of patients with CD (n = 7) compared with those with colon cancer (n = 6). Elevated serum PO levels might serve as a marker for local inflammation and prognosis in patients with CD.
A fragment-based approach identifies an allosteric pocket that impacts malate dehydrogenase activity
Authors: Reyes Romero Atilio , Lunev Serjey , Popowicz Grzegorz M. , Calderone Vito , Gentili Matteo , Sattler Michael , Plewka Jacek , Taube Michał , Kozak Maciej , Holak Tad A. , Dömling Alexander S. S. , Groves Matthew R.
Published: August 2021

Malate dehydrogenases (MDHs) sustain tumor growth and carbon metabolism by pathogens including Plasmodium falciparum. However, clinical success of MDH inhibitors is absent, as current small molecule approaches targeting the active site are unselective. The presence of an allosteric binding site at oligomeric interface allows the development of more specific inhibitors. To this end we performed a differential NMR-based screening of 1500 fragments to identify fragments that bind at the oligomeric interface. Subsequent biophysical and biochemical experiments of an identified fragment indicate an allosteric mechanism of 4-(3,4-difluorophenyl) thiazol-2-amine (4DT) inhibition by impacting the formation of the active site loop, located >30 Å from the 4DT binding site. Further characterization of the more tractable homolog 4-phenylthiazol-2-amine (4PA) and 16 other derivatives are also reported. These data pave the way for downstream development of more selective molecules by utilizing the oligomeric interfaces showing higher species sequence divergence than the MDH active site.
Body centered tetragonal nanoparticle superlattices: why and when they form?
Authors: Missoni Leandro , Tagliazucchi Mario
Published: August 2021

The higher-than-expected stability of the body-centered-tetragonal (BCT) phase in superlattices of alkyl-coated Nanoparticles (NP) is examined with a molecular theory, which explicitly models the ligands on the NP surfaces.