bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the Interaction Between Free‐Living Bacteria and Iron in the Global Ocean
Authors: Pham Anh Le‐Duy , Aumont Olivier , Ratnarajah Lavenia , Tagliabue Alessandro
Published: April 2022

Marine free‐living (FL) bacteria play a key role in the cycling of essential biogeochemical elements, including iron (Fe), during their uptake, transformation and release of organic matter throughout the water column. Similar to phytoplankton, the growth of FL bacteria is regulated by nutritive resources such as Fe, and the low availability of these resources may influence bacterial interactions with phytoplankton, causing knock‐on effects for biogeochemical cycling. Yet, knowledge of the factors limiting the growth of FL bacteria and their role within the Fe cycle is poorly constrained. Here, we explicitly represent FL, carbon‐oxidizing bacteria in a three‐dimensional global ocean biogeochemistry model to address these questions. We find that although Fe can emerge as proximally limiting in the tropical Pacific and in high‐latitude regions during summer, the growth of FL bacteria is ultimately controlled by the availability of labile dissolved organic carbon over most of the world's oceans. In Fe‐limited regions, FL bacterial biomass is sensitive to their Fe uptake capability in seasonally Fe‐limitation regions and to their minimum Fe requirements in regions perennially low in Fe. Fe consumption by FL bacteria is significant in the upper ocean in our model, and their competition with phytoplankton for Fe affects phytoplankton growth dynamics and can make bacteria become more carbon limited. The impact of FL bacteria on the Fe distribution in the ocean interior is small due to a tight coupling between Fe uptake and release. Moving forward, future work that considers other bacteria groups and different bacterial metabolisms is needed to explore the broader role of bacteria in ocean Fe cycling. In this context, the global growing’ omics data from ocean observing programs can play a crucial role.
Analysis of Pacific Hotspot Chains
Authors: Chase A. , Wessel P.
Published: April 2022

Seamount trails created by mantle plumes are often used to establish absolute reference frames for plate motion. When plume drift is considered, changes in seamount trail direction and age progression cannot be attributed to plate motion change alone. Here, improvements to age‐progressive models of eleven Pacific hotspot chains are made independently of plate motion models. Our approach involves bathymetry processing to robustly predict a smooth, continuous hotspot path by connecting maxima in filtered seamount bathymetry, with across‐track uncertainties from seamount trail width and amplitude. Published ages from seamount samples are projected orthogonally onto these paths. We determine best‐fit models of age as functions of along‐track distance, giving continuous age‐progression models for each seamount chain with uncertainties in age and geometry. Different sources of paleolatitudes are examined by incorporating data from the magnetization of seamount drill‐core samples, paleo‐poles from marine magnetic anomaly skewness inversions, and paleo‐spin‐axes inferred from shifts of equatorial sediments. Improved paleolatitude models for the Hawaiian‐Emperor and Louisville chains are determined by combining these different types of data. Paleolatitude models are predicted for other chains during periods when sufficient amounts of paleo‐pole or paleo‐spin‐axis data are available. Analysis of the eleven Pacific seamount chains provide constraints for future plate and plume motion models. We analyze the temporal change in distance between coeval seamounts, reflecting relative drifts between the hotspots at different times in the past. The observed changes imply systematic relative hotspot drifts compatible with paleolatitude trends.
Identifying Hydro‐Sensitive Coral δ18O Records for Improved High‐Resolution Temperature and Salinity Reconstructions
Authors: Thompson D. M. , Conroy J. L. , Konecky B. L. , Stevenson S. , DeLong K. L. , McKay N. , Reed E. , Jonkers L. , Carré M.
Published: April 2022

Stable oxygen isotopic ratios in corals (δ18Ocoral) are commonly utilized to reconstruct climate variability beyond the limit of instrumental observations. These measurements provide constraints on past seawater temperature, due to the thermodynamics of isotopic fractionation, but also past salinity, as both salinity and seawater δ18O (δ18Osw) are similarly affected by precipitation/evaporation, advection, and other processes. We use historical observations, isotope‐enabled model simulations, and the PAGES Iso2k database to assess the potential of δ18Ocoral to provide information on past salinity. Using ‘‘pseudocorals’’ to represent δ18Ocoral as a function of observed or simulated temperature and salinity/δ18Osw, we find that δ18Osw contributes up to 89% of δ18Ocoral variability in the Western Pacific Warm Pool. Although uncertainty in the δ18Osw‐salinity relationship influences the inferred salinity variability, corals from these sites could provide valuable δ18Osw reconstructions. Coordinated in situ monitoring of salinity and δ18Osw is vital for improving estimates of hydroclimatic change.
Ocean Biogeochemical Signatures of the North Pacific Blob
Authors: Mogen Samuel C. , Lovenduski Nicole S. , Dallmann Allysa R. , Gregor Luke , Sutton Adrienne J. , Bograd Steven J. , Quiros Nathali Cordero , Di Lorenzo Emanuele , Hazen Elliott L. , Jacox Michael G. , Buil Mercedes Pozo , Yeager Stephen
Published: April 2022

The Blob was the early manifestation of the Northeast Pacific marine heat wave from 2013 to 2016. While the upper ocean temperature in the Blob has been well described, the impacts on marine biogeochemistry have not been fully studied. Here, we characterize and develop understanding of Eastern North Pacific upper ocean biogeochemical properties during the Winter of 2013–2014 using in situ observations, an observation‐based product, and reconstructions from a collection of ocean models. We find that the Blob is associated with significant upper ocean biogeochemical anomalies: A 5% increase in aragonite saturation state (temporary reprieve of ocean acidification) and a 3% decrease in oxygen concentration (enhanced deoxygenation). Anomalous advection and mixing drive the aragonite saturation anomaly, while anomalous heating and air‐sea gas exchange drive the oxygen anomaly. Marine heatwaves do not necessarily serve as an analog for future change as they may enhance or mitigate long‐term trends.
The Role of Aerosol‐Radiation Interaction in the Meteorology Prediction at the Weather Scale in the Numerical Weather Prediction Model
Authors: Zhang Wenjie , Zhang Xiaoye , Wang Hong
Published: April 2022

The current capabilities of the numerical weather prediction (NWP) model to simulate aerosol‐radiation interaction (ARI) impacts on weather prediction are still rarely considered compared with climate models. Here, the NWP model GRAPES_CUACE is used to evaluate the role of the ARI in meteorology prediction at the weather scale in China. The results show that the online calculation of ARI in the model can extensively improve the meteorology prediction accuracy involving temperature, wind, and pressure at most vertical levels in relatively clean, light, and heavy pollution stages. This improvement significantly occurs in the meteorology factors below 950 hPa prediction such as temperature at 2 m, 1,000, and 950 hPa, and mean sea level pressure, particularly in heavy pollution areas and stages. Unlike temperature, the improvement of ARI in the predicted wind at the height of the boundary layer is more significant than near‐surface. However, this improvement declines when the low‐cloud exists.
Importance of the Antarctic Slope Current in the Southern Ocean Response to Ice Sheet Melt and Wind Stress Change
Authors: Beadling R. L. , Krasting J. P. , Griffies S. M. , Hurlin W. J. , Bronselaer B. , Russell J. L. , MacGilchrist G. A. , Tesdal J.‐E. , Winton M.
Published: April 2022

We use two coupled climate models, GFDL‐CM4 and GFDL‐ESM4, to investigate the physical response of the Southern Ocean to changes in surface wind stress, Antarctic meltwater, and the combined forcing of the two in a pre‐industrial control simulation. The meltwater cools the ocean surface in all regions except the Weddell Sea, where the wind stress warms the near‐surface layer. The limited sensitivity of the Weddell Sea surface layer to the meltwater is due to the spatial distribution of the meltwater fluxes, regional bathymetry, and large‐scale circulation patterns. The meltwater forcing dominates the Antarctic shelf response and the models yield strikingly different responses along West Antarctica. The disagreement is attributable to the mean‐state representation and meltwater‐driven acceleration of the Antarctic Slope Current (ASC). In CM4, the meltwater is efficiently trapped on the shelf by a well resolved, strong, and accelerating ASC which isolates the West Antarctic shelf from warm offshore waters, leading to strong subsurface cooling. In ESM4, a weaker and diffuse ASC allows more meltwater to escape to the open ocean, the West Antarctic shelf does not become isolated, and instead strong subsurface warming occurs. The CM4 results suggest a possible negative feedback mechanism that acts to limit future melting, while the ESM4 results suggest a possible positive feedback mechanism that acts to accelerate melt. Our results demonstrate the strong influence the ASC has on governing changes along the shelf, highlighting the importance of coupling interactive ice sheet models to ocean models that can resolve these dynamical processes.
A versatile interferometric technique for probing the thermophysical properties of complex fluids
Authors: Verma Gopal , Yadav Gyanendra , Saraj Chaudry Sajed , Li Longnan , Miljkovic Nenad , Delville Jean Pierre , Li Wei
Published: April 2022

Laser-induced thermocapillary deformation of liquid surfaces has emerged as a promising tool to precisely characterize the thermophysical properties of pure fluids. However, challenges arise for nanofluid (NF) and soft bio-fluid systems where the direct interaction of the laser generates an intriguing interplay between heating, momentum, and scattering forces which can even damage soft biofluids. Here, we report a versatile, pump-probe-based, rapid, and non-contact interferometric technique that resolves interface dynamics of complex fluids with the precision of ~1 nm in thick-film and 150 pm in thin-film regimes below the thermal limit without the use of lock-in or modulated beams. We characterize the thermophysical properties of complex NF in three exclusively different types of configurations. First, when the NF is heated from the bottom through an opaque substrate, we demonstrate that our methodology permits the measurement of thermophysical properties (viscosity, surface tension, and diffusivity) of complex NF and biofluids. Second, in a top illumination configuration, we show a precise characterization of NF by quantitively isolating the competing forces, taking advantage of the different time scales of these forces. Third, we show the measurement of NF confined in a metal cavity, in which the transient thermoelastic deformation of the metal surface provides the properties of the NF as well as thermo-mechanical properties of the metal. Our results reveal how the dissipative nature of the heatwave allows us to investigate thick-film dynamics in the thin-film regime, thereby suggesting a general approach for precision measurements of complex NFs, biofluids, and optofluidic devices.
Single photon emission and recombination dynamics in self-assembled GaN/AlN quantum dots
Authors: Stachurski Johann , Tamariz Sebastian , Callsen Gordon , Butté Raphaël , Grandjean Nicolas
Published: April 2022

III-nitride quantum dots (QDs) are a promising system actively studied for their ability to maintain single photon emission up to room temperature. Here, we report on the evolution of the emission properties of self-assembled GaN/AlN QDs for temperatures ranging from 5 to 300 K. We carefully track the photoluminescence of a single QD and measure an optimum single photon purity of g(2)(0) = 0.05 ± 0.02 at 5 K and 0.17 ± 0.08 at 300 K. We complement this study with temperature dependent time-resolved photoluminescence measurements (TRPL) performed on a QD ensemble to further investigate the exciton recombination dynamics of such polar zero-dimensional nanostructures. By comparing our results to past reports, we emphasize the complexity of recombination processes in this system. Instead of the more conventional mono-exponential decay typical of exciton recombination, TRPL transients display a bi-exponential feature with short- and long-lived components that persist in the low excitation regime. From the temperature insensitivity of the long-lived excitonic component, we first discard the interplay of dark-to-bright state refilling in the exciton recombination process. Besides, this temperature-invariance also highlights the absence of nonradiative exciton recombinations, a likely direct consequence of the strong carrier confinement observed in GaN/AlN QDs up to 300 K. Overall, our results support the viability of these dots as a potential single-photon source for quantum applications at room temperature.
Metabolomics analysis of post-traumatic stress disorder symptoms in World Trade Center responders
Authors: Kuan Pei-Fen , Yang Xiaohua , Kotov Roman , Clouston Sean , Bromet Evelyn , Luft Benjamin J.
Published: April 2022

Metabolomics has yielded promising insights into the pathophysiology of post-traumatic stress disorder (PTSD). The current study expands understanding of the systems-level effects of metabolites by using global metabolomics and complex lipid profiling in plasma samples from 124 World Trade Center responders (56 PTSD, 68 control) on 1628 metabolites. Differential metabolomics analysis identified hexosylceramide HCER(26:1) associated with PTSD at FDR < 0.1. The multi-metabolite composite score achieved an AUC of 0.839 for PTSD versus unaffected control classification. Independent component analysis identified three metabolomic modules significantly associated with PTSD. These modules were significantly enriched in bile acid metabolism, fatty acid metabolism and pregnenolone steroids, which are involved in innate immunity, inflammatory process and neuronal excitability, respectively. Integrative analysis of metabolomics and our prior proteomics datasets on subsample of 96 responders identified seven proteomic modules significantly correlated with metabolic modules. Overall, our findings shed light on the molecular alterations and identify metabolomic-proteomic signatures associated with PTSD by using machine learning and network approaches to enhance understanding of the pathways implicated in PTSD. If present results are confirmed in follow-up studies, they may inform development of novel treatments.
Chromatin complexes subunit BAP18 promotes triple-negative breast cancer progression through transcriptional activation of oncogene S100A9
Authors: Zhang Yin-Ling , Deng Ling , Liao Li , Yang Shao-Ying , Hu Shu-Yuan , Ning Yan , Zhang Fang-Lin , Li Da-Qiang
Published: April 2022

Triple-negative breast cancer (TNBC) is a highly lethal disease due to aggressive clinical phenotype and the lack of validated therapeutic targets. Our recent quantitative proteomic analysis of 90 cases of TNBC tissues and 72 cases of matched adjacent normal tissues revealed that the expression levels of BPTF-associated protein of 18 KDa (BAP18), a component of the MLL1 and NURF chromatin complexes, were upregulated in TNBC tissues relative to normal tissues. However, the biological function and the underlying mechanism of BAP18 in TNBC progression remain unexplored. Here, we report that BAP18 promoted TNBC cell proliferation, migration, and invasion in vitro and xenograft tumor growth and lung colonization in vivo. Mechanistic investigations revealed that S100 calcium-binding protein A9 (S100A9), a member of the S100 protein family that is frequently upregulated in breast tumors and acts as an oncogenic driver in breast cancer progression, was a downstream target gene of BAP18. BAP18 was recruited to histone H3 trimethylation at lysine 4 (H3K4me3)-marked promoter of S100A9 and enhanced its promoter activities. Notably, knockdown of BAP18 by short hairpin RNA in TNBC cells suppressed xenograft tumor growth in mice, the noted effect was partially reverted by re-expression of S100A9 in BAP18-depleted cells. Taken together, these results suggest that BAP18 promotes TNBC progression through, at least in part, transcriptional activation of oncogene S100A9, and represents a potential therapeutic target for TNBC.
CircMAN1A2 is upregulated by Helicobacter pylori and promotes development of gastric cancer
Authors: Guo Ruiting , Cui Xixi , Li Xue , Zang Wen , Chang Mingjie , Sun Zenghui , Liu Zhifang , Sun Yundong , Jia Jihui , Li Wenjuan
Published: April 2022

Helicobacter pylori (H. pylori) is one of the main causes of gastric cancer. It has been reported that circRNAs play a vital role in the development of multiple types of cancer. However, the role of H. pylori-induced circRNAs in the development of gastric cancer has not been studied. In this study, we found that H. pylori could induce the upregulation of circMAN1A2 in AGS and BGC823 cells independent of CagA. The downregulation of circMAN1A2 could inhibit the proliferation, migration and invasion of gastric cancer cells, and circMAN1A2 could promote the progression of gastric cancer induced by H. pylori by sponging miR-1236-3p to regulate MTA2 expression. Furthermore, circMAN1A2 knockdown inhibited xenograft tumour growth in vivo, and the overexpression of circMAN1A2 was associated with the progression of gastric cancer. Hence, Helicobacter pylori induced circMAN1A2 expression to promote the carcinogenesis of gastric cancer, and circMAN1A2 might be a new potential diagnostic marker and therapeutic target for gastric cancer.
Comprehensive view of microscopic interactions between DNA-coated colloids
Authors: Cui Fan , Marbach Sophie , Zheng Jeana Aojie , Holmes-Cerfon Miranda , Pine David J.
Published: April 2022

The self-assembly of DNA-coated colloids into highly-ordered structures offers great promise for advanced optical materials. However, control of disorder, defects, melting, and crystal growth is hindered by the lack of a microscopic understanding of DNA-mediated colloidal interactions. Here we use total internal reflection microscopy to measure in situ the interaction potential between DNA-coated colloids with nanometer resolution and the macroscopic melting behavior. The range and strength of the interaction are measured and linked to key material design parameters, including DNA sequence, polymer length, grafting density, and complementary fraction. We present a first-principles model that screens and combines existing theories into one coherent framework and quantitatively reproduces our experimental data without fitting parameters over a wide range of DNA ligand designs. Our theory identifies a subtle competition between DNA binding and steric repulsion and accurately predicts adhesion and melting at a molecular level. Combining experimental and theoretical results, our work provides a quantitative and predictive approach for guiding material design with DNA-nanotechnology and can be further extended to a diversity of colloidal and biological systems.
Hypoxia-activated neuropeptide Y/Y5 receptor/RhoA pathway triggers chromosomal instability and bone metastasis in Ewing sarcoma
Authors: Lu Congyi , Mahajan Akanksha , Hong Sung-Hyeok , Galli Susana , Zhu Shiya , Tilan Jason U. , Abualsaud Nouran , Adnani Mina , Chung Stacey , Elmansy Nada , Rodgers Jasmine , Rodriguez Olga , Albanese Christopher , Wang Hongkun , Regan Maureen , Zgonc Valerie , Blancato Jan , Krawczyk Ewa , Gallicano G. Ian , Girgis Michael , Cheema Amrita , Iżycka-Świeszewska Ewa , Cavalli Luciane R. , Pack Svetlana D. , Kitlinska Joanna
Published: April 2022

Adverse prognosis in Ewing sarcoma (ES) is associated with the presence of metastases, particularly in bone, tumor hypoxia and chromosomal instability (CIN). Yet, a mechanistic link between these factors remains unknown. We demonstrate that in ES, tumor hypoxia selectively exacerbates bone metastasis. This process is triggered by hypoxia-induced stimulation of the neuropeptide Y (NPY)/Y5 receptor (Y5R) pathway, which leads to RhoA over-activation and cytokinesis failure. These mitotic defects result in the formation of polyploid ES cells, the progeny of which exhibit high CIN, an ability to invade and colonize bone, and a resistance to chemotherapy. Blocking Y5R in hypoxic ES tumors prevents polyploidization and bone metastasis. Our findings provide evidence for the role of the hypoxia-inducible NPY/Y5R/RhoA axis in promoting genomic changes and subsequent osseous dissemination in ES, and suggest that targeting this pathway may prevent CIN and disease progression in ES and other cancers rich in NPY and Y5R.
Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach
Authors: Richardson Tom G. , Crouch Daniel J. M. , Power Grace M. , Morales-Berstein Fernanda , Hazelwood Emma , Fang Si , Cho Yoonsu , Inshaw Jamie R. J. , Robertson Catherine C. , Sidore Carlo , Cucca Francesco , Rich Steven S. , Todd John A. , Davey Smith George
Published: April 2022

The rising prevalence of childhood obesity has been postulated as an explanation for the increasing rate of individuals diagnosed with type 1 diabetes (T1D). In this study, we use Mendelian randomization (MR) to provide evidence that childhood body size has an effect on T1D risk (OR = 2.05 per change in body size category, 95% CI = 1.20 to 3.50, P = 0.008), which remains after accounting for body size at birth and during adulthood using multivariable MR (OR = 2.32, 95% CI = 1.21 to 4.42, P = 0.013). We validate this direct effect of childhood body size using data from a large-scale T1D meta-analysis based on n = 15,573 cases and n = 158,408 controls (OR = 1.94, 95% CI = 1.21 to 3.12, P = 0.006). We also provide evidence that childhood body size influences risk of asthma, eczema and hypothyroidism, although multivariable MR suggested that these effects are mediated by body size in later life. Our findings support a causal role for higher childhood body size on risk of being diagnosed with T1D, whereas its influence on the other immune-associated diseases is likely explained by a long-term effect of remaining overweight for many years over the lifecourse.
Solid surface frustrated Lewis pair constructed on layered AlOOH for hydrogenation reaction
Authors: Liu Shulin , Dong Minghua , Wu Yuxuan , Luan Sen , Xin Yu , Du Juan , Li Shaopeng , Liu Huizhen , Han Buxing
Published: April 2022

Designing heterogeneous solid surface frustrated Lewis pair (ssFLP) catalyst for hydrogenation is a new challenge in catalysis and no research has been reported on the construction of ssFLP on boehmite (AlOOH) surfaces up to now as far as we know. Herein, AlOOH with a layer structure is prepared and it is found that the Lewis basic OHv site (one H removed from OH) and an adjacent Lewis acidic unsaturated Al site (Al3+unsatur.) proximal to a surface OHv (OH vacancy) on AlOOH layers could form the ssFLP. The layered structure of AlOOH and its abundant OH defects over the surface result in a high concentration of OHv/Al3+unsatur. FLPs, which are conducive to highly efficient hydrogen activation for hydrogenation of olefins and alkynes with low H-H bond dissociates activation energy of 0.16 eV under mild conditions (T = 80°C and P(H2) = 2.0 MPa). This work develops a new kind of hydrogenation catalyst and provides a new perspective for creating solid surface FLP.
Kidney epithelial cells are active mechano-biological fluid pumps
Authors: Choudhury Mohammad Ikbal , Li Yizeng , Mistriotis Panagiotis , Vasconcelos Ana Carina N. , Dixon Eryn E. , Yang Jing , Benson Morgan , Maity Debonil , Walker Rebecca , Martin Leigha , Koroma Fatima , Qian Feng , Konstantopoulos Konstantinos , Woodward Owen M. , Sun Sean X.
Published: April 2022

The role of mechanical forces driving kidney epithelial fluid transport and morphogenesis in kidney diseases is unclear. Here, using a microfluidic platform to recapitulate fluid transport activity of kidney cells, we report that renal epithelial cells can actively generate hydraulic pressure gradients across the epithelium. The fluidic flux declines with increasing hydraulic pressure until a stall pressure, in a manner similar to mechanical fluid pumps. For normal human kidney cells, the fluidic flux is from apical to basal, and the pressure is higher on the basal side. For human Autosomal Dominant Polycystic Kidney Disease cells, the fluidic flux is reversed from basal to apical. Molecular and proteomic studies reveal that renal epithelial cells are sensitive to hydraulic pressure gradients, changing gene expression profiles and spatial arrangements of ion exchangers and the cytoskeleton in different pressure conditions. These results implicate mechanical force and hydraulic pressure as important variables during kidney function and morphological change, and provide insights into pathophysiological mechanisms underlying the development and transduction of hydraulic pressure gradients.
Molecular and functional heterogeneity in dorsal and ventral oligodendrocyte progenitor cells of the mouse forebrain in response to DNA damage
Authors: Boda Enrica , Lorenzati Martina , Parolisi Roberta , Harding Brian , Pallavicini Gianmarco , Bonfanti Luca , Moccia Amanda , Bielas Stephanie , Di Cunto Ferdinando , Buffo Annalisa
Published: April 2022

In the developing mouse forebrain, temporally distinct waves of oligodendrocyte progenitor cells (OPCs) arise from different germinal zones and eventually populate either dorsal or ventral regions, where they present as transcriptionally and functionally equivalent cells. Despite that, developmental heterogeneity influences adult OPC responses upon demyelination. Here we show that accumulation of DNA damage due to ablation of citron-kinase or cisplatin treatment cell-autonomously disrupts OPC fate, resulting in cell death and senescence in the dorsal and ventral subsets, respectively. Such alternative fates are associated with distinct developmental origins of OPCs, and with a different activation of NRF2-mediated anti-oxidant responses. These data indicate that, upon injury, dorsal and ventral OPC subsets show functional and molecular diversity that can make them differentially vulnerable to pathological conditions associated with DNA damage.
An energizing role for motivation in information-seeking during the early phase of the COVID-19 pandemic
Authors: Abir Yaniv , Marvin Caroline B. , van Geen Camilla , Leshkowitz Maya , Hassin Ran R. , Shohamy Daphna
Published: April 2022

The COVID-19 pandemic has highlighted the importance of understanding and managing information seeking behavior. Information-seeking in humans is often viewed as irrational rather than utility maximizing. Here, we hypothesized that this apparent disconnect between utility and information-seeking is due to a latent third variable, motivation. We quantified information-seeking, learning, and COVID-19-related concern (which we used as a proxy for motivation regarding COVID-19 and the changes in circumstance it caused) in a US-based sample (n = 5376) during spring 2020. We found that self-reported levels of COVID-19 concern were associated with directed seeking of COVID-19-related content and better memory for such information. Interestingly, this specific motivational state was also associated with a general enhancement of information-seeking for content unrelated to COVID-19. These effects were associated with commensurate changes to utility expectations and were dissociable from the influence of non-specific anxiety. Thus, motivation both directs and energizes epistemic behavior, linking together utility and curiosity.
Kronos scRT: a uniform framework for single-cell replication timing analysis
Authors: Gnan Stefano , Josephides Joseph M. , Wu Xia , Spagnuolo Manuela , Saulebekova Dalila , Bohec Mylène , Dumont Marie , Baudrin Laura G. , Fachinetti Daniele , Baulande Sylvain , Chen Chun-Long
Published: April 2022

Mammalian genomes are replicated in a cell type-specific order and in coordination with transcription and chromatin organization. Currently, single-cell replication studies require individual processing of sorted cells, yielding a limited number (<100) of cells. Here, we develop Kronos scRT, a software for single-cell Replication Timing (scRT) analysis. Kronos scRT does not require a specific platform or cell sorting, which allows investigating large datasets obtained from asynchronous cells. By applying our tool to published data as well as droplet-based single-cell whole-genome sequencing data generated in this study, we exploit scRT from thousands of cells for different mouse and human cell lines. Our results demonstrate that although genomic regions are frequently replicated around their population average RT, replication can occur stochastically throughout S phase. Altogether, Kronos scRT allows fast and comprehensive investigations of the RT programme at the single-cell resolution for both homogeneous and heterogeneous cell populations.
Metabolic preference assay for rapid diagnosis of bloodstream infections
Authors: Rydzak Thomas , Groves Ryan A. , Zhang Ruichuan , Aburashed Raied , Pushpker Rajnigandha , Mapar Maryam , Lewis Ian A.
Published: April 2022

Bloodstream infections (BSIs) cause >500,000 infections and >80,000 deaths per year in North America. The length of time between the onset of symptoms and administration of appropriate antimicrobials is directly linked to mortality rates. It currently takes 2–5 days to identify BSI pathogens and measure their susceptibility to antimicrobials – a timeline that directly contributes to preventable deaths. To address this, we demonstrate a rapid metabolic preference assay (MPA) that uses the pattern of metabolic fluxes observed in ex-vivo microbial cultures to identify common pathogens and determine their antimicrobial susceptibility profiles. In a head-to-head race with a leading platform (VITEK 2, BioMérieux) used in diagnostic laboratories, MPA decreases testing timelines from 40 hours to under 20. If put into practice, this assay could reduce septic shock mortality and reduce the use of broad spectrum antibiotics.
Enhancement of anaerobic glycolysis – a role of PGC-1α4 in resistance exercise
Authors: Koh Jin-Ho , Pataky Mark W. , Dasari Surendra , Klaus Katherine A. , Vuckovic Ivan , Ruegsegger Gregory N. , Kumar Arathi Prabha , Robinson Matthew M. , Nair K. Sreekumaran
Published: April 2022

Resistance exercise training (RET) is an effective countermeasure to sarcopenia, related frailty and metabolic disorders. Here, we show that an RET-induced increase in PGC-1α4 (an isoform of the transcriptional co-activator PGC-1α) expression not only promotes muscle hypertrophy but also enhances glycolysis, providing a rapid supply of ATP for muscle contractions. In human skeletal muscle, PGC-1α4 binds to the nuclear receptor PPARβ following RET, resulting in downstream effects on the expressions of key glycolytic genes. In myotubes, we show that PGC-1α4 overexpression increases anaerobic glycolysis in a PPARβ-dependent manner and promotes muscle glucose uptake and fat oxidation. In contrast, we found that an acute resistance exercise bout activates glycolysis in an AMPK-dependent manner. These results provide a mechanistic link between RET and improved glucose metabolism, offering an important therapeutic target to counteract aging and inactivity-induced metabolic diseases benefitting those who cannot exercise due to many reasons.
Glycaemic control is associated with SARS-CoV-2 breakthrough infections in vaccinated patients with type 2 diabetes
Authors: Marfella Raffaele , Sardu Celestino , D’Onofrio Nunzia , Prattichizzo Francesco , Scisciola Lucia , Messina Vincenzo , La Grotta Rosalba , Balestrieri Maria Luisa , Maggi Paolo , Napoli Claudio , Ceriello Antonio , Paolisso Giuseppe
Published: April 2022

Patients with type 2 diabetes (T2D) are characterized by blunted immune responses, which are affected by glycaemic control. Whether glycaemic control influences the response to COVID-19 vaccines and the incidence of SARS-CoV-2 breakthrough infections is unknown. Here we show that poor glycaemic control, assessed as mean HbA1c in the post-vaccination period, is associated with lower immune responses and an increased incidence of SARS-CoV-2 breakthrough infections in T2D patients vaccinated with mRNA-BNT162b2. We report data from a prospective observational study enroling healthcare and educator workers with T2D receiving the mRNA-BNT162b2 vaccine in Campania (Italy) and followed for one year (5 visits, follow-up 346 ± 49 days) after one full vaccination cycle. Considering the 494 subjects completing the study, patients with good glycaemic control (HbA1c one-year mean < 7%) show a higher virus-neutralizing antibody capacity and a better CD4 + T/cytokine response, compared with those with poor control (HbA1c one-year mean ≥ 7%). The one-year mean of HbA1c is linearly associated with the incidence of breakthrough infections (Beta = 0.068; 95% confidence interval [CI], 0.032-0.103; p < 0.001). The comparison of patients with poor and good glycaemic control through Cox regression also show an increased risk for patients with poor control (adjusted hazard ratio [HR], 0.261; 95% CI, 0.097-0.700; p = 0.008). Among other factors, only smoking (HR = 0.290, CI 0.146-0.576 for non-smokers; p < 0.001) and sex (HR = 0.105, CI 0.035-0.317 for females; p < 0.001) are significantly associated with the incidence of breakthrough infections.
Accuracy prompts are a replicable and generalizable approach for reducing the spread of misinformation
Authors: Pennycook Gordon , Rand David G.
Published: April 2022

Interventions that shift users attention toward the concept of accuracy represent a promising approach for reducing misinformation sharing online. We assess the replicability and generalizability of this accuracy prompt effect by meta-analyzing 20 experiments (with a totalN = 26,863) completed by our group between 2017 and 2020. This internal meta-analysis includes all relevant studies regardless of outcome and uses identical analyses across all studies. Overall, accuracy prompts increased the quality of news that people share (sharing discernment) relative to control, primarily by reducing sharing intentions for false headlines by 10% relative to control in these studies. The magnitude of the effect did not significantly differ by content of headlines (politics compared with COVID-19 related news) and did not significantly decay over successive trials. The effect was not robustly moderated by gender, race, political ideology, education, or value explicitly placed on accuracy, but was significantly larger for older, more reflective, and more attentive participants. This internal meta-analysis demonstrates the replicability and generalizability of the accuracy prompt effect on sharing discernment.
Risk factors for severe COVID-19 differ by age for hospitalized adults
Authors: Molani Sevda , Hernandez Patricia V. , Roper Ryan T. , Duvvuri Venkata R. , Baumgartner Andrew M. , Goldman Jason D. , Ertekin-Taner Nilüfer , Funk Cory C. , Price Nathan D. , Rappaport Noa , Hadlock Jennifer J.
Published: April 2022

Risk stratification for hospitalized adults with COVID-19 is essential to inform decisions about individual patients and allocation of resources. So far, risk models for severe COVID outcomes have included age but have not been optimized to best serve the needs of either older or younger adults. Models also need to be updated to reflect improvements in COVID-19 treatments. This retrospective study analyzed data from 6906 hospitalized adults with COVID-19 from a community health system across five states in the western United States. Risk models were developed to predict mechanical ventilation illness or death across one to 56 days of hospitalization, using clinical data available within the first hour after either admission with COVID-19 or a first positive SARS-CoV-2 test. For the seven-day interval, models for age ≥ 18 and < 50 years reached AUROC 0.81 (95% CI 0.71–0.91) and models for age ≥ 50 years reached AUROC 0.82 (95% CI 0.77–0.86). Models revealed differences in the statistical significance and relative predictive value of risk factors between older and younger patients including age, BMI, vital signs, and laboratory results. In addition, for hospitalized patients, sex and chronic comorbidities had lower predictive value than vital signs and laboratory results.
Temporal and sex-dependent gene expression patterns in a renal ischemia–reperfusion injury and recovery pig model
Authors: Nemours Stéphane , Castro Luis , Ribatallada-Soriano Didac , Semidey Maria E. , Aranda Miguel , Ferrer Marina , Sanchez Alex , Morote Joan , Cantero-Recasens Gerard , Meseguer Anna
Published: April 2022

Men are more prone to acute kidney injury (AKI) and chronic kidney disease (CKD), progressing to end-stage renal disease (ESRD) than women. Severity and capacity to regenerate after AKI are important determinants of CKD progression, and of patient morbidity and mortality in the hospital setting. To determine sex differences during injury and recovery we have generated a female and male renal ischemia/reperfusion injury (IRI) pig model, which represents a major cause of AKI. Although no differences were found in blood urea nitrogen (BUN) and serum creatinine (SCr) levels between both sexes, females exhibited higher mononuclear infiltrates at basal and recovery, while males showed more tubular damage at injury. Global transcriptomic analyses of kidney biopsies from our IRI pig model revealed a sexual dimorphism in the temporal regulation of genes and pathways relevant for kidney injury and repair, which was also detected in human samples. Enrichment analysis of gene sets revealed five temporal and four sexual patterns governing renal IRI and recovery. Overall, this study constitutes an extensive characterization of the time and sex differences occurring during renal IRI and recovery at gene expression level and offers a template of translational value for further study of sexual dimorphism in kidney diseases.
An Arabidopsis mutant deficient in phosphatidylinositol-4-phosphate kinases ß1 and ß2 displays altered auxin-related responses in roots
Authors: Starodubtseva Anastasiia , Kalachova Tetiana , Retzer Katarzyna , Jelínková Adriana , Dobrev Petre , Lacek Jozef , Pospíchalová Romana , Angelini Jindřiška , Guivarc’h Anne , Pateyron Stéphanie , Soubigou-Taconnat Ludivine , Burketová Lenka , Ruelland Eric
Published: April 2022

Phosphatidylinositol 4-kinases (PI4Ks) are the first enzymes that commit phosphatidylinositol into the phosphoinositide pathway. Here, we show that Arabidopsis thaliana seedlings deficient in PI4Kβ1 and β2 have several developmental defects including shorter roots and unfinished cytokinesis. The pi4kβ1β2 double mutant was insensitive to exogenous auxin concerning inhibition of root length and cell elongation; it also responded more slowly to gravistimulation. The pi4kß1ß2 root transcriptome displayed some similarities to a wild type plant response to auxin. Yet, not all the genes displayed such a constitutive auxin-like response. Besides, most assessed genes did not respond to exogenous auxin. This is consistent with data with the transcriptional reporter DR5-GUS. The content of bioactive auxin in the pi4kß1ß2 roots was similar to that in wild-type ones. Yet, an enhanced auxin-conjugating activity was detected and the auxin level reporter DII-VENUS did not respond to exogenous auxin in pi4kß1ß2 mutant. The mutant exhibited altered subcellular trafficking behavior including the trapping of PIN-FORMED 2 protein in rapidly moving vesicles. Bigger and less fragmented vacuoles were observed in pi4kß1ß2 roots when compared to the wild type. Furthermore, the actin filament web of the pi4kß1ß2 double mutant was less dense than in wild-type seedling roots, and less prone to rebuilding after treatment with latrunculin B. A mechanistic model is proposed in which an altered PI4K activity leads to actin filament disorganization, changes in vesicle trafficking, and altered auxin homeostasis and response resulting in a pleiotropic root phenotypes.
The mycobacterial desaturase DesA2 is associated with mycolic acid biosynthesis
Authors: Bailo Rebeca , Radhakrishnan Anjana , Singh Albel , Nakaya Makoto , Fujiwara Nagatoshi , Bhatt Apoorva
Published: April 2022

Mycolic acids are critical for the survival and virulence of Mycobacterium tuberculosis, the causative agent of tuberculosis. Double bond formation in the merochain of mycolic acids remains poorly understood, though we have previously shown desA1, encoding an aerobic desaturase, is involved in mycolic acid desaturation. Here we show that a second desaturase encoded by desA2 is also involved in mycolate biosynthesis. DesA2 is essential for growth of the fast-growing Mycobacterium smegmatis in laboratory media. Conditional depletion of DesA2 led to a decrease in mycolic acid biosynthesis and loss of mycobacterial viability. Additionally, DesA2-depleted cells also accumulated fatty acids of chain lengths C19-C24. The complete loss of mycolate biosynthesis following DesA2 depletion, and the absence of any monoenoic derivatives (found to accumulate on depletion of DesA1) suggests an early role for DesA2 in the mycolic acid biosynthesis machinery, highlighting its potential as a drug target.
Dominant transcript expression profiles of human protein-coding genes interrogated with GTEx dataset
Authors: Tung Kuo-Feng , Pan Chao-Yu , Lin Wen-chang
Published: April 2022

The discovery and quantification of mRNA transcripts using short-read next-generation sequencing (NGS) data is a complicated task. There are far more alternative mRNA transcripts expressed by human genes than can be identified from NGS transcriptome data and various bioinformatic pipelines, while the numbers of annotated human protein-coding genes has gradually declined in recent years. It is essential to learn more about the thorough tissue expression profiles of alternative transcripts in order to obtain their molecular modulations and actual functional significance. In this report, we present a bioinformatic database for interrogating the representative tissue of human protein-coding transcripts. The database allows researchers to visually explore the top-ranked transcript expression profiles in particular tissue types. Most transcripts of protein-coding genes were found to have certain tissue expression patterns. This observation demonstrated that many alternative transcripts were particularly modulated in different cell types. This user-friendly tool visually represents transcript expression profiles in a tissue-specific manner. Identification of tissue specific protein-coding genes and transcripts is a substantial advance towards interpreting their biological functions and further functional genomics studies.
The time-course of feature-based attention effects dissociated from temporal expectation and target-related processes
Authors: Moerel Denise , Grootswagers Tijl , Robinson Amanda K. , Shatek Sophia M. , Woolgar Alexandra , Carlson Thomas A. , Rich Anina N.
Published: April 2022

Selective attention prioritises relevant information amongst competing sensory input. Time-resolved electrophysiological studies have shown stronger representation of attended compared to unattended stimuli, which has been interpreted as an effect of attention on information coding. However, because attention is often manipulated by making only the attended stimulus a target to be remembered and/or responded to, many reported attention effects have been confounded with target-related processes such as visual short-term memory or decision-making. In addition, attention effects could be influenced by temporal expectation about when something is likely to happen. The aim of this study was to investigate the dynamic effect of attention on visual processing using multivariate pattern analysis of electroencephalography (EEG) data, while (1) controlling for target-related confounds, and (2) directly investigating the influence of temporal expectation. Participants viewed rapid sequences of overlaid oriented grating pairs while detecting a “target” grating of a particular orientation. We manipulated attention, one grating was attended and the other ignored (cued by colour), and temporal expectation, with stimulus onset timing either predictable or not. We controlled for target-related processing confounds by only analysing non-target trials. Both attended and ignored gratings were initially coded equally in the pattern of responses across EEG sensors. An effect of attention, with preferential coding of the attended stimulus, emerged approximately 230 ms after stimulus onset. This attention effect occurred even when controlling for target-related processing confounds, and regardless of stimulus onset expectation. These results provide insight into the effect of feature-based attention on the dynamic processing of competing visual information.
Strength training alters the tissue fatty acids profile and slightly improves the thermogenic pathway in the adipose tissue of obese mice
Authors: de Melo Diego Gomes , Anaruma Chadi Pellegrini , da Cruz Rodrigues Kellen Cristina , Pereira Rodrigo Martins , de Campos Thais Dantis Pereira , Canciglieri Raphael Santos , Ramos Camila Oliveira , Cintra Dennys Esper , Ropelle Eduardo Rochete , da Silva Adelino Sanchez Ramos , Pauli José Rodrigo , de Moura Leandro Pereira
Published: April 2022

Obesity is a disease characterized by the exacerbated increase of adipose tissue. A possible way to decrease the harmful effects of excessive adipose tissue is to increase the thermogenesis process, to the greater energy expenditure generated by the increase in heat in the body. In adipose tissue, the thermogenesis process is the result of an increase in mitochondrial work, having as substrate H+ ions, and which is related to the increased activity of UCP1. Evidence shows that stress is responsible for increasing the greater induction of UCP1 expression via β-adrenergic receptors. It is known that physical exercise is an important implement for sympathetic stimulation promoting communication between norepinephrine/epinephrine with membrane receptors. Thus, the present study investigates the influence of short-term strength training (STST) on fatty acid composition, lipolysis, lipogenesis, and browning processes in the subcutaneous adipose tissue (sWAT) of obese mice. For this, Swiss mice were divided into three groups: lean control, obesity sedentary, and obese strength training (OBexT). Obese animals were fed a high-fat diet for 14 weeks. Trained obese animals were submitted to 7 days of strength exercise. It was demonstrated that STST sessions were able to reduce fasting glycemia. In the sWAT, the STST was able to decrease the levels of the long-chain fatty acids profile, saturated fatty acid, and palmitic fatty acid (C16:0). Moreover, it was showed that STST did not increase protein levels responsible for lipolysis, the ATGL, ABHD5, pPLIN1, and pHSL. On the other hand, the exercise protocol decreased the expression of the lipogenic enzyme SCD1. Finally, our study demonstrated that the STST increased browning process-related genes such as PGC-1α, PRDM16, and UCP1 in the sWAT. Interestingly, all these biomolecular mechanisms have been observed independently of changes in body weight. Therefore, it is concluded that short-term strength exercise can be an effective strategy to initiate morphological changes in sWAT.