bluuebunny/crossref_metadata_2025 huggingface dataset:
A new conceptual framework for the transformation of groundwater dissolved organic matter
Authors: McDonough Liza K. , Andersen Martin S. , Behnke Megan I. , Rutlidge Helen , Oudone Phetdala , Meredith Karina , O’Carroll Denis M. , Santos Isaac R. , Marjo Christopher E. , Spencer Robert G. M. , McKenna Amy M. , Baker Andy
Published: April 2022

Groundwater comprises 95% of the liquid fresh water on Earth and contains a diverse mix of dissolved organic matter (DOM) molecules which play a significant role in the global carbon cycle. Currently, the storage times and degradation pathways of groundwater DOM are unclear, preventing an accurate estimate of groundwater carbon sources and sinks for global carbon budgets. Here we reveal the transformations of DOM in aging groundwater using ultra-high resolution mass spectrometry combined with radiocarbon dating. Long-term anoxia and a lack of photodegradation leads to the removal of oxidised DOM and a build-up of both reduced photodegradable formulae and aerobically biolabile formulae with a strong microbial signal. This contrasts with the degradation pathway of DOM in oxic marine, river, and lake systems. Our findings suggest that processes such as groundwater extraction and subterranean groundwater discharge to oceans could result in up to 13 Tg of highly photolabile and aerobically biolabile groundwater dissolved organic carbon released to surface environments per year, where it can be rapidly degraded. These findings highlight the importance of considering groundwater DOM in global carbon budgets.
Economic shocks predict increases in child wasting prevalence
Authors: Headey Derek D. , Ruel Marie T.
Published: April 2022

In low and middle income countries macroeconomic volatility is common, and severe negative economic shocks can substantially increase poverty and food insecurity. Less well understood are the implications of these contractions for child acute malnutrition (wasting), a major risk factor for under-5 mortality. This study explores the nutritional impacts of economic growth shocks over 1990–2018 by linking wasting outcomes collected for 1.256 million children from 52 countries to lagged annual changes in economic growth. Estimates suggest that a 10% annual decline in national income increases moderate/severe wasting prevalence by 14.4–17.8%. An exploration of possible mechanisms suggests negative economic shocks may increase risks of inadequate dietary diversity among children. Applying these results to the latest economic growth estimates for 2020 suggests that COVID-19 could put an additional 9.4 million preschoolers at risk of wasting, net of the effects of preventative policy actions.
TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer
Authors: Su Zhangli , Monshaugen Ida , Wilson Briana , Wang Fengbin , Klungland Arne , Ougland Rune , Dutta Anindya
Published: April 2022

RNA modifications are important regulatory elements of RNA functions. However, most genome-wide mapping of RNA modifications has focused on messenger RNAs and transfer RNAs, but such datasets have been lacking for small RNAs. Here we mapped N1-methyladenosine (m1A) in the cellular small RNA space. Benchmarked with synthetic m1A RNAs, our workflow identified specific groups of m1A-containing small RNAs, which are otherwise disproportionally under-represented. In particular, 22-nucleotides long 3′ tRNA-fragments are highly enriched for TRMT6/61A-dependent m1A located within the seed region. TRMT6/61A-dependent m1A negatively affects gene silencing by tRF-3s. In urothelial carcinoma of the bladder, where TRMT6/61A is over-expressed, higher m1A modification on tRFs is detected, correlated with a dysregulation of tRF targetome. Lastly, TRMT6/61A regulates tRF-3 targets involved in unfolded protein response. Together, our results reveal a mechanism of regulating gene expression via base modification of small RNA.
Metabolic plasticity can amplify ecosystem responses to global warming
Authors: Kordas Rebecca L. , Pawar Samraat , Kontopoulos Dimitrios-Georgios , Woodward Guy , O’Gorman Eoin J.
Published: April 2022

Organisms have the capacity to alter their physiological response to warming through acclimation or adaptation, but the consequence of this metabolic plasticity for energy flow through food webs is currently unknown, and a generalisable framework does not exist for modelling its ecosystem-level effects. Here, using temperature-controlled experiments on stream invertebrates from a natural thermal gradient, we show that the ability of organisms to raise their metabolic rate following chronic exposure to warming decreases with increasing body size. Chronic exposure to higher temperatures also increases the acute thermal sensitivity of whole-organismal metabolic rate, independent of body size. A mathematical model parameterised with these findings shows that metabolic plasticity could account for 60% higher ecosystem energy flux with just +2 °C of warming than a traditional model based on ecological metabolic theory. This could explain why long-term warming amplifies ecosystem respiration rates through time in recent mesocosm experiments, and highlights the need to embed metabolic plasticity in predictive models of global warming impacts on ecosystems.
Neutron-upscattering enhancement of the triple-alpha process
Authors: Bishop J. , Parker C. E. , Rogachev G. V. , Ahn S. , Koshchiy E. , Brandenburg K. , Brune C. R. , Charity R. J. , Derkin J. , Dronchi N. , Hamad G. , Jones-Alberty Y. , Kokalova Tz. , Massey T. N. , Meisel Z. , Ohstrom E. V. , Paneru S. N. , Pollacco E. C. , Saxena M. , Singh N. , Smith R. , Sobotka L. G. , Soltesz D. , Subedi S. K. , Voinov A. V. , Warren J. , Wheldon C.
Published: April 2022

The neutron inelastic scattering of carbon-12, populating the Hoyle state, is a reaction of interest for the triple-alpha process. The inverse process (neutron upscattering) can enhance the Hoyle state’s decay rate to the bound states of 12C, effectively increasing the overall triple-alpha reaction rate. The cross section of this reaction is impossible to measure experimentally but has been determined here at astrophysically-relevant energies using detailed balance. Using a highly-collimated monoenergetic beam, here we measure neutrons incident on the Texas Active Target Time Projection Chamber (TexAT TPC) filled with CO2 gas, we measure the 3α-particles (arising from the decay of the Hoyle state following inelastic scattering) and a cross section is extracted. Here we show the neutron-upscattering enhancement is observed to be much smaller than previously expected. The importance of the neutron-upscattering enhancement may therefore not be significant aside from in very particular astrophysical sites (e.g. neutron star mergers).
Vasa nucleates asymmetric translation along the mitotic spindle during unequal cell divisions
Authors: Fernandez-Nicolas Ana , Uchida Alicia , Poon Jessica , Yajima Mamiko
Published: April 2022

mRNA translation on the spindle is hypothesized to be an essential strategy for the localized production of cell regulators. This mechanism may be important particularly in early embryonic cells, which have a large diffusion volume and that undergo rapid cell divisions. Evidence to test such a hypothesis has been, however, limited. Here, we use an embryo with both symmetric and asymmetric cell divisions and manipulate Vasa protein, an RNA-helicase, on the spindle in live sea urchin embryos. We learned that the spindle serves as a major site of translation and that protein synthesis within a single spindle can be unequal and help drive asymmetric cell divisions during embryogenesis. Recruiting Vasa to the ectopic sub-cellular region induced a new site of translation, disturbed asymmetric translation on the spindle, and changed the cell fate. Based on these observations, we conclude that Vasa functions in localized translation, which provides a spatiotemporal control in protein synthesis and is essential for rapidly developing embryonic cells.
RNA polymerase II pausing factor NELF in CD8+ T cells promotes antitumor immunity
Authors: Wu Bogang , Zhang Xiaowen , Chiang Huai-Chin , Pan Haihui , Yuan Bin , Mitra Payal , Qi Leilei , Simonyan Hayk , Young Colin N. , Yvon Eric , Hu Yanfen , Zhang Nu , Li Rong
Published: April 2022

T cell factor 1 (TCF1) is required for memory and stem-like CD8+ T cell functions. How TCF1 partners with other transcription factors to regulate transcription remains unclear. Here we show that negative elongation factor (NELF), an RNA polymerase II (Pol II) pausing factor, cooperates with TCF1 in T cell responses to cancer. Deletion of mouse Nelfb, which encodes the NELFB subunit, in mature T lymphocytes impairs immune responses to both primary tumor challenge and tumor antigen-mediated vaccination. Nelfb deletion causes more exhausted and reduced memory T cell populations, whereas its ectopic expression boosts antitumor immunity and efficacy of chimeric antigen receptor T-cell immunotherapy. Mechanistically, NELF is associated with TCF1 and recruited preferentially to the enhancers and promoters of TCF1 target genes. Nelfb ablation reduces Pol II pausing and chromatin accessibility at these TCF1-associated loci. Our findings thus suggest an important and rate-limiting function of NELF in anti-tumor immunity.
Photoinduced evolution of lattice orthorhombicity and conceivably enhanced ferromagnetism in LaMnO3 membranes
Authors: Lu Qinwen , Cheng Yun , Wu Lijun , Guo Hongli , Qi Fengfeng , Zhang Haijuan , Yu Junxiao , Liu Qixin , Wang Qing , Liang Genhao , Chen Jie , Lu Yalin , Zhang Jie , Xiang Dao , Zhao Jin , Zhu Yimei , Zhai Xiaofang
Published: April 2022

Ultrashort laser pulses have been utilized to dynamically drive phase transitions in correlated quantum materials. Of particular interest is whether phases not achievable in thermal equilibrium can be induced in complex oxides with intricately coupled lattice, electron and spin degrees of freedom. Here, we tracked atomic motions in LaMnO3 following photoexcitation with MeV ultrafast electron diffraction (MeV-UED) technique. We found that the light excited state exhibits numerous signatures different from thermal equilibrium ones, including nearly conserved Bragg intensities, strongly suppressed La cation and oxygen anion displacements, and the long-range lattice orthorhombicity evolution. Furthermore, using first-principles calculations, we predict that the ferromagnetic ordering and conductivity are both enhanced upon laser excitation due to the reduction of the lattice orthorhombicity. This work benefits from recent advance in fabrication of membrane films with high epitaxial quality and in MeV-UED with large momentum space access and high temporal resolution.
Neural activation during emotional interference corresponds to emotion dysregulation in stressed teachers
Authors: Fynes-Clinton Samuel , Sherwell Chase , Ziaei Maryam , York Ashley , O’Connor Emma Sanders , Forrest Kylee , Flynn Libby , Bower Julie , Reutens David , Carroll Annemaree
Published: April 2022

Teacher stress and burnout has been associated with low job satisfaction, reduced emotional wellbeing, and poor student learning outcomes. Prolonged stress is associated with emotion dysregulation and has thus become a focus of stress interventions. This study examines emotional interference effects in a group of teachers suffering from high stress and to explore how individual differences in cognitive control, emotion dysregulation, and emotion recognition related to patterns of neural activation. Forty-nine teachers suffering moderate-high stress participated in an emotional counting Stroop task while their brain activity was imaged using functional magnetic resonance imaging. Participants viewed general or teacher specific words of either negative or neutral valence and were required to count the number of words on screen. Behavioural and neuroimaging results suggest that teachersareable to control emotional responses to negative stimuli, as no evidence of emotional interference was detected. However, patterns of neural activation revealed early shared engagement of regions involved in cognitive reappraisal during negative task conditions and unique late engagement of the hippocampus only while counting teacher-specific negative words. Further, we identified that greater emotion dysregulation was associated with increased activation of regions involved in cognitive control processes during neutral word trials. Teachers who showed slower emotion recognition performance were also found to have greater activation in regions associated with visual and word processing, specifically during the teacher specific negative word condition of the task. Future research should explore emotion regulation strategy use in teachers and utilise temporally sensitive neuroimaging techniques to further understand these findings.
Intron-mediated induction of phenotypic heterogeneity
Authors: Lukačišin Martin , Espinosa-Cantú Adriana , Bollenbach Tobias
Published: April 2022

Intragenic regions that are removed during maturation of the RNA transcript—introns—are universally present in the nuclear genomes of eukaryotes1. The budding yeast, an otherwise intron-poor species, preserves two sets of ribosomal protein genes that differ primarily in their introns2,3. Although studies have shed light on the role of ribosomal protein introns under stress and starvation4–6, understanding the contribution of introns to ribosome regulation remains challenging. Here, by combining isogrowth profiling7with single-cell protein measurements8, we show that introns can mediate inducible phenotypic heterogeneity that confers a clear fitness advantage. Osmotic stress leads to bimodal expression of the small ribosomal subunit protein Rps22B, which is mediated by an intron in the 5′ untranslated region of its transcript. The two resulting yeast subpopulations differ in their ability to cope with starvation. Low levels of Rps22B protein result in prolonged survival under sustained starvation, whereas high levels of Rps22B enable cells to grow faster after transient starvation. Furthermore, yeasts growing at high concentrations of sugar, similar to those in ripe grapes, exhibit bimodal expression of Rps22B when approaching the stationary phase. Differential intron-mediated regulation of ribosomal protein genes thus provides a way to diversify the population when starvation threatens in natural environments. Our findings reveal a role for introns in inducing phenotypic heterogeneity in changing environments, and suggest that duplicated ribosomal protein genes in yeast contribute to resolving the evolutionary conflict between precise expression control and environmental responsiveness9.
Opening of glutamate receptor channel to subconductance levels
Authors: Yelshanskaya Maria V. , Patel Dhilon S. , Kottke Christopher M. , Kurnikova Maria G. , Sobolevsky Alexander I.
Published: April 2022

Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that open their pores in response to binding of the agonist glutamate1–3. An ionic current through a single iGluR channel shows up to four discrete conductance levels (O1–O4)4–6. Higher conductance levels have been associated with an increased number of agonist molecules bound to four individual ligand-binding domains (LBDs)6–10. Here we determine structures of a synaptic complex of AMPA-subtype iGluR and the auxiliary subunit γ2 in non-desensitizing conditions with various occupancy of the LBDs by glutamate. We show that glutamate binds to LBDs of subunits B and D only after it is already bound to at least the same number of LBDs that belong to subunits A and C. Our structures combined with single-channel recordings, molecular dynamics simulations and machine-learning analysis suggest that channel opening requires agonist binding to at least two LBDs. Conversely, agonist binding to all four LBDs does not guarantee maximal channel conductance and favours subconductance states O1 and O2, with O3 and O4 being rare and not captured structurally. The lack of subunit independence and low efficiency coupling of glutamate binding to channel opening underlie the gating of synaptic complexes to submaximal conductance levels, which provide a potential for upregulation of synaptic activity.
Modeling of lophotrichous bacteria reveals key factors for swimming reorientation
Authors: Park Jeungeun , Kim Yongsam , Lee Wanho , Lim Sookkyung
Published: April 2022

Lophotrichous bacteria swim through fluid by rotating their flagellar bundle extended collectively from one pole of the cell body. Cells experience modes of motility such as push, pull, and wrapping, accompanied by pauses of motor rotation in between. We present a mathematical model of a lophotrichous bacterium and investigate the hydrodynamic interaction of cells to understand their swimming mechanism. We classify the swimming modes which vary depending on the bending modulus of the hook and the magnitude of applied torques on the motor. Given the hook’s bending modulus, we find that there exist corresponding critical thresholds of the magnitude of applied torques that separate wrapping from pull in CW motor rotation, and overwhirling from push in CCW motor rotation, respectively. We also investigate reoriented directions of cells in three-dimensional perspectives as the cell experiences different series of swimming modes. Our simulations show that the transition from a wrapping mode to a push mode and pauses in between are key factors to determine a new path and that the reoriented direction depends upon the start time and duration of the pauses. It is also shown that the wrapping mode may help a cell to escape from the region where the cell is trapped near a wall.
Genomic evaluation of hybridization in historic and modern North American Bison (Bison bison)
Authors: Stroupe Sam , Forgacs David , Harris Andrew , Derr James N. , Davis Brian W.
Published: April 2022

During the late nineteenth century North American bison underwent a significant population bottleneck resulting in a reduction in population size of over 99% and a species-level near-extinction event. Factors responsible for this destruction included indiscriminate killing, loss of access to suitable habitat, and diseases. At the nadir of this population crash, very few wild plains bison survived and were restricted to Yellowstone National Park, USA and a small number of wild wood bison remained in Wood Buffalo National Park, Canada. However, most surviving bison in the late 1800’s were maintained by cattle ranchers in private herds where hybridization between bison with various breeds of domestic cattle was often encouraged. Over the last 20 years, the legacy of this introgression has been identified using mitochondrial DNA and limited nuclear microsatellite analyses. However, no genome-wide assessment has been performed, and some herds were believed to be free of introgression based on current genetic testing strategies. Herein, we report detailed analyses using whole genome sequencing from nineteen modern and six historical bison, chosen to represent the major lineages of bison, to identify and quantitate signatures of nuclear introgression in their recent (within 200 years) history. Both low and high coverage genomes provided evidence for recent introgression, including animals from Yellowstone, Wind Cave, and Elk Island National Parks which were previously thought to be free from hybridization with domestic cattle. We employed multiple approaches, including one developed for this work, to identify putative cattle haplotypes in each bison genome. These regions vary greatly in size and frequency by sample and herd, though we detected domestic cattle introgression in all bison genomes tested. Since our sampling strategy spanned across the diversity of modern bison populations, these finding are best explained by multiple historical hybridization events between these two species with significant genetic recombination over the last 200 years. Our results demonstrate that whole genome sequencing approaches are required to accurately quantitate cattle introgression in bison.
The protein folding rate and the geometry and topology of the native state
Authors: Wang Jason , Panagiotou Eleni
Published: April 2022

Proteins fold in 3-dimensional conformations which are important for their function. Characterizing the global conformation of proteins rigorously and separating secondary structure effects from topological effects is a challenge. New developments in applied knot theory allow to characterize the topological characteristics of proteins (knotted or not). By analyzing a small set of two-state and multi-state proteins with no knots or slipknots, our results show that 95.4% of the analyzed proteins have non-trivial topological characteristics, as reflected by the second Vassiliev measure, and that the logarithm of the experimental protein folding rate depends on both the local geometry and the topology of the protein’s native state.
Night work, chronotype and cortisol at awakening in female hospital employees
Authors: Burek Katarzyna , Rabstein Sylvia , Kantermann Thomas , Vetter Céline , Rotter Markus , Wang-Sattler Rui , Lehnert Martin , Pallapies Dirk , Jöckel Karl-Heinz , Brüning Thomas , Behrens Thomas
Published: April 2022

To examine the effect of night shift on salivary cortisol at awakening (C1), 30 min later (C2), and on the cortisol awakening response (CAR, the difference between C2 and C1). We compared shift and non-shift workers with a focus on the impact of worker chronotype. Our study included 66 shift-working females (mean age = 37.3 years, SD = 10.2) and 21 non-shift working females (mean age = 47.0 years, SD = 8.9). The shift workers collected their saliva samples at C1 and C2 on each two consecutive day shifts and night shifts. Non-shift workers collected their samples on two consecutive day shifts. We applied linear mixed-effects models (LMM) to determine the effect of night shift on CAR and log-transformed C1 and C2 levels. LMMs were stratified by chronotype group. Compared to non-shift workers, shift workers before day shifts (i.e. after night sleep) showed lower cortisol at C1 (exp $$(\widehat{\beta })$$

(

β
^

)

=0.58, 95% CI 0.42, 0.81) but not at C2. In shift workers, the CARs after night shifts (i.e. after day sleep) were lower compared to CARs before day shifts ($$\widehat{\beta }$$

β
^

= − 11.07, 95% CI − 15.64, − 6.50). This effect was most pronounced in early chronotypes (early: $$\widehat{\beta }$$

β
^

= − 16.61, 95% CI − 27.87, − 5.35; intermediate: $$\widehat{\beta }$$

β
^

= − 11.82, 95% CI − 18.35, − 5.29; late: $$\widehat{\beta }$$

β
^

= − 6.27, 95% CI − 14.28, 1.74). Chronotype did not modify the association between night shift and CAR. In our population of shift workers, there was a mismatch between time of waking up and their natural cortisol peak at waking up (CAR) both during day and night shift duties.
Investigation of breast cancer microstructure and microvasculature from time-dependent DWI and CEST in correlation with histological biomarkers
Authors: Someya Yuko , Iima Mami , Imai Hirohiko , Yoshizawa Akihiko , Kataoka Masako , Isoda Hiroyoshi , Le Bihan Denis , Nakamoto Yuji
Published: April 2022

We investigated the associations of time-dependent DWI, non-Gaussian DWI, and CEST parameters with histological biomarkers in a breast cancer xenograft model. 22 xenograft mice (7 MCF-7 and 15 MDA-MB-231) were scanned at 4 diffusion times [Td = 2.5/5 ms with 11 b-values (0–600 s/mm2) and Td = 9/27.6 ms with 17 b-values (0–3000 s/mm2), respectively]. The apparent diffusion coefficient (ADC) was estimated using 2 b-values in different combinations (ADC0–600 using b = 0 and 600 s/mm2 and shifted ADC [sADC200–1500] using b = 200 and 1500 s/mm2) at each of those diffusion times. Then the change (Δ) in ADC/sADC between diffusion times was evaluated. Non-Gaussian diffusion and intravoxel incoherent motion (IVIM) parameters (ADC0, the virtual ADC at b = 0; K, Kurtosis from non-Gaussian diffusion; f, the IVIM perfusion fraction) were estimated. CEST images were acquired and the amide proton transfer signal intensity (APT SI) were measured. The ΔsADC9–27.6 (between $${\text{sADC}}_{{9\,{\text{ms}}}}^{200{-}1500}$$

sADC

9

ms

200
-
1500

and $${\text{sADC}}_{{27.6\,{\text{ms}}}}^{200{-}1500}$$

sADC

27.6

ms

200
-
1500

and ΔADC2.5_sADC27.6 (between $${\text{ADC}}_{{2.5\, {\text{ms}}}}^{0{-}600}$$

ADC

2.5

ms

0
-
600

and $${\text{sADC}}_{{27.6\,{\text{ms}}}}^{200{-}1500}$$

sADC

27.6

ms

200
-
1500

) was significantly larger for MCF-7 groups, and ΔADC2.5_sADC27.6 was positively correlated with Ki67max and APT SI. ADC0 decreased significantly in MDA-MB-231 group and K increased significantly with Td in MCF-7 group. APT SI and cellular area had a moderately strong positive correlation in MDA-MB-231 and MCF-7 tumors combined, and there was a positive correlation in MDA-MB-231 tumors. There was a significant negative correlation between APT SI and the Ki-67-positive ratio in MDA-MB-231 tumors and when combined with MCF-7 tumors. The associations of ΔADC2.5_sADC27.6 and API SI with Ki-67 parameters indicate that the Td-dependent DW and CEST parameters are useful to predict the histological markers of breast cancers.
Peer presence increases the prosocial behavior of adolescents by speeding the evaluation of outcomes for others
Authors: Sullivan Nicolette J. , Li Rosa , Huettel Scott A.
Published: April 2022

Peer presence can elicit maladaptive adolescent decision-making, potentially by increasing sensitivity to the rewards one receives. It remains unknown whether peer presence also increases adolescents’ sensitivity to others’ outcomes, which could have an adaptive effect in contexts allowing pro-social behaviors. Here, we combine social utility modeling and real-time decision process modeling to characterize how peer presence alters adolescents’ processing of self and other outcomes. We found that adolescents behaved selfishly when privately allocating monetary rewards for themselves and a peer in an incentive-compatible task. In peer presence, however, adolescents became more altruistic. Real-time decision process estimates collected using computer mouse tracking showed that altruistic behavior was associated with relatively earlier influence of peer-outcomes relative to self-outcomes, and that peer presence sped the influence of peer-outcomes without altering the time at which self-outcomes began to influence the decision process. Our results indicate a mechanism through which peer presence prompts greater prosocial behavior by altering how adolescents process prosocial outcomes.
miR-1227-3p participates in the development of fetal growth restriction via regulating trophoblast cell proliferation and apoptosis
Authors: Cui Jiawen , Kang Xinyi , Shan Yanxing , Zhang Mingjin , Gao Ying , Wu Wei , Chen Liping
Published: April 2022

Fetal growth restriction (FGR) is a common obstetric disease, which is harmful to the pregnant women and fetuses. It has many influencing factors, but the specific etiology is not clear. MiRNA plays an important role in the fetal growth and development. In this article, we use TaqMan Low-Density Array to screen and analyze the differently expressed miRNAs in FGR-affected placenta (n = 40) and the normal placenta (n = 40). A total of 139 abnormally expressed miRNAs in the FGR-affected placenta were identified, and miR-1227-3p was the most highly downregulated miRNA. Importantly, miR-1227-3p may promote the proliferation in HTR-8/SVneo cells, while inhibited the apoptosis of HTR-8/SVneo cells. DAVID was used to analyze the pathway enrichment of target genes of miR-1227-3p to predict its mechanism of action. Furthermore, the putative targets of miR-1227-3p were predicted using the TargetScan, PicTar, DIANA LAB, and miRWalk database. The potential expression of target genes of miR-1227-3p, including PRKAB2, AKT1, PIK3R3, and MKNK1 were significantly increased in FGR-affected placenta. Taken together, miR-1227-3p may participate in the development of FGR via regulating trophoblast cell proliferation and apoptosis by targeting genes involved in the insulin pathway. MiR-1227-3p may have a potential clinical value in the prevention and treatment of FGR, we need to study further to prove its value in the future.
Subthalamic nucleus deep brain stimulation driven by primary motor cortex γ2 activity in parkinsonian monkeys
Authors: Darbin Olivier , Hatanaka Nobuhiko , Takara Sayuki , Kaneko Nobuya , Chiken Satomi , Naritoku Dean , Martino Anthony , Nambu Atsushi
Published: April 2022

In parkinsonism, subthalamic nucleus (STN) electrical deep brain stimulation (DBS) improves symptoms, but may be associated with side effects. Adaptive DBS (aDBS), which enables modulation of stimulation, may limit side effects, but limited information is available about clinical effectiveness and efficaciousness. We developed a brain-machine interface for aDBS, which enables modulation of stimulation parameters of STN-DBS in response to γ2 band activity (80-200 Hz) of local field potentials (LFPs) recorded from the primary motor cortex (M1), and tested its effectiveness in parkinsonian monkeys. We trained two monkeys to perform an upper limb reaching task and rendered them parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Bipolar intracortical recording electrodes were implanted in the M1, and a recording chamber was attached to access the STN. In aDBS, the M1 LFPs were recorded, filtered into the γ2 band, and discretized into logic pulses by a window discriminator, and the pulses were used to modulate the interval and amplitude of DBS pulses. In constant DBS (cDBS), constant stimulus intervals and amplitudes were used. Reaction and movement times during the task were measured and compared between aDBS and cDBS. The M1-γ2 activities were increased before and during movements in parkinsonian monkeys and these activities modulated the aDBS pulse interval, amplitude, and dispersion. With aDBS and cDBS, reaction and movement times were significantly decreased in comparison to DBS-OFF. The electric charge delivered was lower with aDBS than cDBS. M1-γ2 aDBS in parkinsonian monkeys resulted in clinical benefits that did not exceed those from cDBS. However, M1-γ2 aDBS achieved this magnitude of benefit for only two thirds of the charge delivered by cDBS. In conclusion, M1-γ2 aDBS is an effective therapeutic approach which requires a lower electrical charge delivery than cDBS for comparable clinical benefits.
Human forager response to abrupt climate change at 8.2 ka on the Atlantic coast of Europe
Authors: García-Escárzaga Asier , Gutiérrez-Zugasti Igor , Marín-Arroyo Ana B. , Fernandes Ricardo , Núñez de la Fuente Sara , Cuenca-Solana David , Iriarte Eneko , Simões Carlos , Martín-Chivelet Javier , González-Morales Manuel R. , Roberts Patrick
Published: April 2022

The cooling and drying associated with the so-called ‘8.2 ka event’ have long been hypothesized as having sweeping implications for human societies in the Early Holocene, including some of the last Mesolithic hunter-gatherers in Atlantic Europe. Nevertheless, detailed ‘on-site’ records with which the impacts of broader climate changes on human-relevant environments can be explored have been lacking. Here, we reconstruct sea surface temperatures (SST) from δ18O values measured on subfossil topshells Phorcus lineatus exploited by the Mesolithic human groups that lived at El Mazo cave (N Spain) between 9 and 7.4 ka. Bayesian modelling of 65 radiocarbon dates, in combination with this δ18O data, provide a high-resolution seasonal record of SST, revealing that colder SST during the 8.2 ka event led to changes in the availability of different shellfish species. Intensification in the exploitation of molluscs by humans indicates demographic growth in these Atlantic coastal settings which acted as refugia during this cold event.
Optogenetic activation of the diaphragm
Authors: Benevides Ethan S. , Sunshine Michael D. , Rana Sabhya , Fuller David D.
Published: April 2022

Impaired diaphragm activation is common in many neuromuscular diseases. We hypothesized that expressing photoreceptors in diaphragm myofibers would enable light stimulation to evoke functional diaphragm activity, similar to endogenous bursts. In a mouse model, adeno-associated virus (AAV) encoding channelrhodopsin-2 (AAV9-CAG-ChR2-mVenus, 6.12 × 1011 vg dose) was delivered to the diaphragm using a minimally invasive method of microinjection to the intrapleural space. At 8–18 weeks following AAV injection, mice were anesthetized and studied during spontaneous breathing. We first showed that diaphragm electromyographic (EMG) potentials could be evoked with brief presentations of light, using a 473 nm high intensity LED. Evoked potential amplitude increased with intensity or duration of the light pulse. We next showed that in a paralyzed diaphragm, trains of light pulses evoked diaphragm EMG activity which resembled endogenous bursting, and this was sufficient to generate respiratory airflow. Light-evoked diaphragm EMG bursts showed no diminution after up to one hour of stimulation. Histological evaluation confirmed transgene expression in diaphragm myofibers. We conclude that intrapleural delivery of AAV9 can drive expression of ChR2 in the diaphragm and subsequent photostimulation can evoke graded compound diaphragm EMG activity similar to endogenous inspiratory bursting.
Exhaled nitric oxide in early rheumatoid arthritis and effects of methotrexate treatment
Authors: Weitoft Tomas , Lind Anders , Larsson Anders , Rönnelid Johan , Högman Marieann
Published: April 2022

Patients with established rheumatoid arthritis (RA) and disease modifying treatments have lower nitric oxide (NO) levels in the alveolar compartment (CANO) and in the airway wall (CawNO), but also higher diffusion capacities for NO in the airways (DawNO) compared to matched controls. The aim of the present study was to investigate the NO lung dynamics in patients with recent onset RA before and after immune suppression with methotrexate therapy. Patients with early RA and antibodies against anticitrullinated peptides (ACPA) were recruited. Measurement of exhaled NO and inflammatory markers in serum were performed. Clinical disease activity was evaluated with Disease Activity Score for 28 joints. Healthy individuals were used as matched controls. Data are presented as median (lower quartile, upper quartile) values. RA patients (n = 44) had lower exhaled NO (FENO50) 16 (10–24) ppb compared to controls 21 (15, 29) ppb, p = 0.013. In NO-dynamics, CANO was lower in RA patients 1.6 (1.0, 2.2) ppb compared to the control subjects 2.3 (1.3, 3.1) ppb, p = 0.007. CawNO was also lower in the RA patients 55 (24, 106) ppb compared to control subjects 124 (110, 170) ppb, p < 0.001, but DawNO was higher 17 (8, 30) mL/s and 9 (5, 11) mL/s respectively, p < 0.001. Methotrexate treatment for three months reduced disease activity, but did not change the NO dynamics. In conclusion, the altered NO dynamics of the lung in ACPA-positive RA patients are already present in the early stages of the disease before any treatments and do not change after methotrexate therapy suggesting a role in the pathogenesis.
Error rate reduction of single-qubit gates via noise-aware decomposition into native gates
Authors: Maldonado Thomas J. , Flick Johannes , Krastanov Stefan , Galda Alexey
Published: April 2022

In the current era of Noisy Intermediate-Scale Quantum (NISQ) technology, the practical use of quantum computers remains inhibited by our inability to aptly decouple qubits from their environment to mitigate computational errors. In this paper, we introduce an approach by which knowledge of a qubit’s initial quantum state and the standard parameters describing its decoherence can be leveraged to mitigate the noise present during the execution of a single-qubit gate. We benchmark our protocol using cloud-based access to IBM quantum processors. On , we demonstrate a reduction of the single-qubit error rate by 38%, from $$1.6 \times 10 ^{-3}$$

1.6
×

10

-
3

to $$1.0 \times 10 ^{-3}$$

1.0
×

10

-
3

, provided the initial state of the input qubit is known. On , we prove that our protocol will never decrease gate fidelity, provided the system’s $$T_1$$

T
1

and $$T_2$$

T
2

times have not drifted above 100 times their assumed values. The protocol can be used to reduce quantum state preparation errors, as well as to improve the fidelity of quantum circuits for which some knowledge of the qubits’ intermediate states can be inferred. This paper presents a pathway to using information about noise levels and quantum state distributions to significantly reduce error rates associated with quantum gates via optimized decomposition into native hardware gates.
Role of the anterior insular cortex in restraint-stress induced fear behaviors
Authors: Park Sanggeon , Cho Jeiwon , Huh Yeowool
Published: April 2022

Anxiety disorders, such as post-traumatic stress disorder (PTSD), are thought to occur by dysfunction in the fear and anxiety-related brain circuit, however, the exact mechanisms remain unknown. Recent human studies have shown that the right anterior insular cortex (aIC) activity is positively correlated with the severity of PTSD symptoms. Understanding the role of the aIC in fear and anxiety may provide insights into the etiology of anxiety disorders. We used a modified shock-probe defensive burying behavioral test, which utilizes the natural propensity of rodents to bury potentially dangerous objects, to test the role of aIC in fear. Mice exposed to restraint stress exhibited burying of the restrainer-resembling object, indicative of defensive behavior. Electrolytic ablation of the aIC significantly diminished this defensive burying behavior, suggesting the involvement of the aIC. Single-unit recording of pyramidal neurons in the aIC showed that a proportion of neurons which increased activity in the presence of a restrainer-resembling object was significantly correlated with the defensive burying behavior. This correlation was only present in mice exposed to restraint stress. These results suggest that altered neuronal representation in the aIC may regulate fear and anxiety after exposure to a traumatic event. Overall, our result demonstrates that the aIC mediates fear and anxiety and that it could be a potential target for treating anxiety disorders.
Storage and release of rare earth elements in microsphere-based scaffolds for enhancing osteogenesis
Authors: Xu Weikang , Wei Kun , Lin Zefeng , Wu Tingting , Li Guixiang , Wang Liyan
Published: April 2022

In osteoporosis and diabetes, it is essential to accelerate the bone repair and regeneration process. Trace rare earth elements such as lanthanum (La) ions (La3+) with appropriate concentrations are bioactive and can effectively regulate bone tissue performances. However, few well-established bone tissue engineering scaffolds can precisely and stably release La3+to promote bone regeneration significantly. Based on the advantages of biodegradable microspheres and microsphere-based scaffolds for controlled drug release, we developed poly(lactide-co-glycolide) (PLGA)-based microsphere-based scaffolds as both three-dimensional (3D) porous scaffolds and La3+storage and release systems for osteogenesis. So far, there is no study about microsphere-based scaffolds to release trace La3+to induce osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs). PLGA microspheres co-embedded with La-doped mesoporous silica (LMS) with different amounts of doped La were sintered to prepare the LMS/PLGA (LMSP) microsphere-based scaffold. The La3+release behavior of LMSP can be controlled by adjusting the doping amount of La in mesoporous silica (MS). All these scaffolds possessed a 3D network architecture. With the increase of La doping, LMSP can better compensate for the pH decrease caused by PLGA degradation. The combination of MS and PLGA can avoid the cytotoxicity of MS alone. All prepared LMSP scaffolds were non-cytotoxic. After BMSCs were implanted on scaffolds, LMSP could promote cells adhesion, proliferation, and osteogenic differentiation. Among these microsphere-based scaffolds, LMSP-3 with stable and higher dose La3+release behavior showed the strongest ability to enhance the osteogenesis of BMSCs. The results showed that microsphere-based scaffolds with the ability to store and stably control the release of La3+could effectively improve osteogenic performance, which provides a new idea for the construction of bone tissue engineering scaffolds.
The Arabidopsis effector-triggered immunity landscape is conserved in oilseed crops
Authors: Breit-McNally Clare , Desveaux Darrell , Guttman David S.
Published: April 2022

The bacterial phytopathogen Pseudomonas syringae causes disease on a wide array of plants, including the model plant Arabidopsis thaliana and its agronomically important relatives in the Brassicaceae family. To cause disease, P. syringae delivers effector proteins into plant cells through a type III secretion system. In response, plant nucleotide-binding leucine-rich repeat proteins recognize specific effectors and mount effector-triggered immunity (ETI). While ETI is pervasive across A. thaliana, with at least 19 families of P. syringae effectors recognized in this model species, the ETI landscapes of crop species have yet to be systematically studied. Here, we investigated the conservation of the A. thaliana ETI landscape in two closely related oilseed crops, Brassica napus (canola) and Camelina sativa (false flax). We show that the level of immune conservation is inversely related to the degree of evolutionary divergence from A. thaliana, with the more closely related C. sativa losing ETI responses to only one of the 19 P. syringae effectors tested, while the more distantly related B. napus loses ETI responses to four effectors. In contrast to the qualitative conservation of immune response, the quantitative rank order is not as well-maintained across the three species and diverges increasingly with evolutionary distance from A. thaliana. Overall, our results indicate that the A. thaliana ETI profile is qualitatively conserved in oilseed crops, but quantitatively distinct.
Indoor green wall affects health-associated commensal skin microbiota and enhances immune regulation: a randomized trial among urban office workers
Authors: Soininen L. , Roslund M. I. , Nurminen N. , Puhakka R. , Laitinen O. H. , Hyöty H. , Sinkkonen A. ,   ADELE research group, Cerrone Damiano , Grönroos Mira , Hui Nan , Luukkonen Anna , Mäkelä Iida , Nurminen Noora , Oikarinen Sami , Parajuli Anirudra , Puhakka Riikka , Roslund Marja I. , Saarenpää Mika , Soininen Laura , Sun Yan , Vari Heli K. , Laitinen Olli H. , Rajaniemi Juho , Hyoty Heikki , Sinkkonen Aki
Published: April 2022

Urbanization reduces microbiological abundance and diversity, which has been associated with immune mediated diseases. Urban greening may be used as a prophylactic method to restore microbiological diversity in cities and among urbanites. This study evaluated the impact of air-circulating green walls on bacterial abundance and diversity on human skin, and on immune responses determined by blood cytokine measurements. Human subjects working in offices in two Finnish cities (Lahti and Tampere) participated in a two-week intervention, where green walls were installed in the rooms of the experimental group. Control group worked without green walls. Skin and blood samples were collected before (Day0), during (Day14) and two weeks after (Day28) the intervention. The relative abundance of genus Lactobacillus and the Shannon diversity of phylum Proteobacteria and class Gammaproteobacteria increased in the experimental group. Proteobacterial diversity was connected to the lower proinflammatory cytokine IL-17A level among participants in Lahti. In addition, the change in TGF-β1 levels was opposite between the experimental and control group. As skin Lactobacillus and the diversity of Proteobacteria and Gammaproteobacteria are considered advantageous for skin health, air-circulating green walls may induce beneficial changes in a human microbiome. The immunomodulatory potential of air-circulating green walls deserves further research attention.
Evaluation of a seven gene mutational profile as a prognostic factor in a population-based study of clear cell renal cell carcinoma
Authors: van de Pol Jeroen A. A. , Ferronika Paranita , Westers Helga , van Engeland Manon , Terpstra Martijn M. , Smits Kim M. , de Lange Kim , van den Brandt Piet A. , Sijmons Rolf H. , Schouten Leo J. , Kok Klaas
Published: April 2022

In this study, we investigate the influence of the seven genes (VHL, PBRM1, SETD2, BAP1, KDM5C, MTORandTP53) most frequently mutated in clear cell renal cell cancer (ccRCC) on cancer-specific survival (CSS) in the prospective Netherlands Cohort Study on diet and cancer. DNA isolated from routinely archived formalin-fixed paraffin-embedded tumour blocks from 252 incident ccRCC cases was available for targeted next generation sequencing. Based on the sequencing quality and the completeness of information on clinical characteristics and follow-up, we could use 110 cases for survival analysis. The association with CSS for each mutated gene in these cases was tested using multivariable Cox proportional hazards models to estimate hazards ratios (HR) and confidence intervals (CIs), and we observed mutations in one or more of the seven genes in 64 out of 110 cases (58%). In the multivariable-adjusted analyses, mutations inVHLandPBRM1were associated with better CSS (HRs (95% CI) 0.34 (0.13‒0.89) and 0.17 (0.04–0.66), respectively), although these results were not statistically significant after multiple testing correction. No association was observed for the other five genes, which may be attributable to limited power.
Multiplex structural variant detection by whole-genome mapping and nanopore sequencing
Authors: Uppuluri Lahari , Wang Yilin , Young Eleanor , Wong Jessica S. , Abid Heba Z. , Xiao Ming
Published: April 2022

Identification of structural variants (SVs) breakpoints is important in studying mutations, mutagenic causes, and functional impacts. Next-generation sequencing and whole-genome optical mapping are extensively used in SV discovery and characterization. However, multiple platforms and computational approaches are needed for comprehensive analysis, making it resource-intensive and expensive. Here, we propose a strategy combining optical mapping and cas9-assisted targeted nanopore sequencing to analyze SVs. Optical mapping can economically and quickly detect SVs across a whole genome but does not provide sequence-level information or precisely resolve breakpoints. Furthermore, since only a subset of all SVs is known to affect biology, we attempted to type a subset of all SVs using targeted nanopore sequencing. Using our approach, we resolved the breakpoints of five deletions, five insertions, and an inversion, in a single experiment.