bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prenatal earthquake stress exposure in different gestational trimesters is associated with methylation changes in the glucocorticoid receptor gene (NR3C1) and long-term working memory in adulthood
Authors: Wang Ran , Wang Jincheng , Xu Shuqi , Wang Lan , Song Mei , An Cuixia , Wang Xueyi 
Published: April 2022

AbstractPrenatal stress exposure is thought to affect the long-term development of the foetal brain via the HPA axis and to change health outcomes in adulthood, including working memory (WM). The potential mechanism is that there is a critical period of brain development of the foetus, which is a result of selective adaptation to the external environment. The human glucocorticoid gene (NR3C1) is associated with memory and cognition. This study investigates the association between earthquake stress during pregnancy and CpG methylation of the NR3C1 exon 1Fpromoter and its influence on working memory in adulthood. DNA methylation analysis using bisulfite sequencing PCR was quantified in 176 subjects who were exposed or not exposed to intrauterine earthquake and were divided into three groups based on the pregnancy trimester. The Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) were used to assess working memory performance. The methylated NR3C1 exon 1Fpromoter of the prenatal earthquake exposure (PEE) group was significantly higher than that of the control group (CN). Analysis of subgroups indicated that the subjects in the second trimester of PEE group showed significantly higher methylation than those in the third trimester. Significantly low BVMT-R scores were detected in those who experienced prenatal earthquake in the second trimester of PEE group. Methylated CpG site 1 may play a critical role in contributing to lower BVMT-R scores in the second trimester in the PEE group, and may offer a potential epigenetic mechanism that links prenatal stress and long-term effects on working memory.
Midkine noncanonically suppresses AMPK activation through disrupting the LKB1-STRAD-Mo25 complex
Authors: Xia Tian , Chen Di , Liu Xiaolong , Qi Huan , Wang Wen , Chen Huan , Ling Ting , Otkur Wuxiyar , Zhang Chen-Song , Kim Jongchan , Lin Sheng-Cai , Piao Hai-long 
Published: April 2022

AbstractMidkine (MDK), a secreted growth factor, regulates signal transduction and cancer progression by interacting with receptors, and it can be internalized into the cytoplasm by endocytosis. However, its intracellular function and signaling regulation remain unclear. Here, we show that intracellular MDK interacts with LKB1 and STRAD to disrupt the LKB1-STRAD-Mo25 complex. Consequently, MDK decreases the activity of LKB1 to dampen both the basal and stress-induced activation of AMPK by glucose starvation or treatment of 2-DG. We also found that MDK accelerates cancer cell proliferation by inhibiting the activation of the LKB1-AMPK axis. In human cancers, compared to other well-known growth factors, MDK expression is most significantly upregulated in cancers, especially in liver, kidney and breast cancers, correlating with clinical outcomes and inversely correlating with phosphorylated AMPK levels. Our study elucidates an inhibitory mechanism for AMPK activation, which is mediated by the intracellular MDK through disrupting the LKB1-STRAD-Mo25 complex.
Reference-free cell type deconvolution of multi-cellular pixel-resolution spatially resolved transcriptomics data
Authors: Miller Brendan F. , Huang Feiyang , Atta Lyla , Sahoo Arpan , Fan Jean 
Published: April 2022

AbstractRecent technological advancements have enabled spatially resolved transcriptomic profiling but at multi-cellular pixel resolution, thereby hindering the identification of cell-type-specific spatial patterns and gene expression variation. To address this challenge, we develop STdeconvolve as a reference-free approach to deconvolve underlying cell types comprising such multi-cellular pixel resolution spatial transcriptomics (ST) datasets. Using simulated as well as real ST datasets from diverse spatial transcriptomics technologies comprising a variety of spatial resolutions such as Spatial Transcriptomics, 10X Visium, DBiT-seq, and Slide-seq, we show that STdeconvolve can effectively recover cell-type transcriptional profiles and their proportional representation within pixels without reliance on external single-cell transcriptomics references. STdeconvolve provides comparable performance to existing reference-based methods when suitable single-cell references are available, as well as potentially superior performance when suitable single-cell references are not available. STdeconvolve is available as an open-source R software package with the source code available athttps://github.com/JEFworks-Lab/STdeconvolve.
Mechanism of integrin activation by talin and its cooperation with kindlin
Authors: Lu Fan , Zhu Liang , Bromberger Thomas , Yang Jun , Yang Qiannan , Liu Jianmin , Plow Edward F. , Moser Markus , Qin Jun 
Published: April 2022

AbstractTalin-induced integrin binding to extracellular matrix ligands (integrin activation) is the key step to trigger many fundamental cellular processes including cell adhesion, cell migration, and spreading. Talin is widely known to use its N-terminal head domain (talin-H) to bind and activate integrin, but how talin-H operates in the context of full-length talin and its surrounding remains unknown. Here we show that while being capable of inducing integrin activation, talin-H alone exhibits unexpectedly low potency versus a constitutively activated full-length talin. We find that the large C-terminal rod domain of talin (talin-R), which otherwise masks the integrin binding site on talin-H in inactive talin, dramatically enhances the talin-H potency by dimerizing activated talin and bridging it to the integrin co-activator kindlin-2 via the adaptor protein paxillin. These data provide crucial insight into the mechanism of talin and its cooperation with kindlin to promote potent integrin activation, cell adhesion, and signaling.
The role of shear dynamics in biofilm formation
Authors: Tsagkari Erifyli , Connelly Stephanie , Liu Zhaowei , McBride Andrew , Sloan William T. 
Published: April 2022

AbstractThere is growing evidence that individual bacteria sense and respond to changes in mechanical loading. However, the subtle responses of multispecies biofilms to dynamic fluid shear stress are not well documented because experiments often fail to disentangle any beneficial effects of shear stress from those delivered by convective transport of vital nutrients. We observed the development of biofilms with lognormally distributed microcolony sizes in drinking water on the walls of flow channels underflow regimes of increasing complexity. First, where regular vortices induced oscillating wall shear and simultaneously enhanced mass transport, which produced the thickest most extensive biofilms. Second, where unsteady uniform flow imposed an oscillating wall shear, with no enhanced transport, and where the biomass and coverage were only 20% smaller. Finally, for uniform steady flows with constant wall shear where the extent, thickness, and density of the biofilms were on average 60% smaller. Thus, the dynamics of shear stress played a significant role in promoting biofilm development, over and above its magnitude or mass transfer effects, and therefore, mechanosensing may prevail in complex multispecies biofilms which could open up new ways of controlling biofilm structure.
Age and sex effects across the blood proteome after ionizing radiation exposure can bias biomarker screening and risk assessment
Authors: Langen Britta , Vorontsov Egor , Spetz Johan , Swanpalmer John , Sihlbom Carina , Helou Khalil , Forssell-Aronsson Eva 
Published: April 2022

AbstractMolecular biomarkers of ionizing radiation (IR) exposure are a promising new tool in various disciplines: they can give necessary information for adaptive treatment planning in cancer radiotherapy, enable risk projection for radiation-induced survivorship diseases, or facilitate triage and intervention in radiation hazard events. However, radiation biomarker discovery has not yet resolved the most basic features of personalized medicine: age and sex. To overcome this critical bias in biomarker identification, we quantitated age and sex effects and assessed their relevance in the radiation response across the blood proteome. We used high-throughput mass spectrometry on blood plasma collected 24 h after 0.5 Gy total body irradiation (15 MV nominal photon energy) from male and female C57BL/6 N mice at juvenile (7-weeks-old) or adult (18-weeks-old) age. We also assessed sex and strain effects using juvenile male and female BALB/c nude mice. We showed that age and sex created significant effects in the proteomic response regarding both extent and functional quality of IR-induced responses. Furthermore, we found that age and sex effects appeared non-linear and were often end-point specific. Overall, age contributed more to differences in the proteomic response than sex, most notably in immune responses, oxidative stress, and apoptotic cell death. Interestingly, sex effects were pronounced for DNA damage and repair pathways and associated cellular outcome (pro-survival vs. pro-apoptotic). Only one protein (AHSP) was identified as a potential general biomarker candidate across age and sex, while GMNN, REG3B, and SNCA indicated some response similarity across age. This low yield advocated that unisex or uniage biomarker screening approaches are not feasible. In conclusion, age- and sex-specific screening approaches should be implemented as standard protocol to ensure robustness and diagnostic power of biomarker candidates. Bias-free molecular biomarkers are a necessary progression towards personalized medicine and integral for advanced adaptive cancer radiotherapy and risk assessment.
Trends in female breast cancer incidence, mortality, and survival in Austria, with focus on age, stage, and birth cohorts (1983–2017)
Authors: Ilic Lazo , Haidinger Gerald , Simon Judit , Hackl Monika , Schernhammer Eva , Papantoniou Kyriaki 
Published: April 2022

AbstractBreast cancer (BC) is the most commonly diagnosed malignant disease and the leading cause of cancer death in women in Austria. We investigated overall and subgroup-specific female breast cancer rates to provide a comprehensive analysis of trends over several decades. Incidence, mortality, and survival, as well as age-, stage-, and birth cohort-specific incidence were analysed using nationwide cancer registry data on 163,694 cases of female breast cancer in Austria (1983–2017). Annual percentage changes were estimated using joinpoint regression. BC incidence underwent linear increases until 1997 and reversed with statistically non-significant declines until 2017. After initial increases in BC-specific mortality, rates were stable from 1989 through 1995 and started declining thereafter, although statistically non-significantly after 2011. Overall BC-specific survivals, as well as survivals according to the calendar period of diagnosis, increased throughout the observation period. Incidence in younger women (aged 44 and lower) showed linear increases, whereas for women aged 45 and higher mostly stable or decreasing rates were observed. Localised BC incidence increased markedly and started declining only in 2012. Distant disease-BC incidence decreased through the whole observation period and incidence of regionalised BC started declining in 2000. Birth cohort-specific incidence peaked in women born between 1935 and 1949 (ages 45–74). In conclusion, the incidence of BC in younger women is increasing, while overall female BC incidence and mortality are stable with non-significant declines. Further, increases in the incidence of early-stage BC (localised) seem disproportionately high in comparison to more modest decreases in late-stage BC incidence (regionalised and distant disease).
Comprehensive decoding mental processes from Web repositories of functional brain images
Authors: Menuet Romuald , Meudec Raphael , Dockès Jérôme , Varoquaux Gael , Thirion Bertrand 
Published: April 2022

AbstractAssociating brain systems with mental processes requires statistical analysis of brain activity across many cognitive processes. These analyses typically face a difficult compromise between scope—from domain-specific to system-level analysis—and accuracy. Using all the functional Magnetic Resonance Imaging (fMRI) statistical maps of the largest data repository available, we trained machine-learning models that decode the cognitive concepts probed in unseen studies. For this, we leveraged two comprehensive resources: NeuroVault—an open repository of fMRI statistical maps with unconstrained annotations—and Cognitive Atlas—an ontology of cognition. We labeled NeuroVault images with Cognitive Atlas concepts occurring in their associated metadata. We trained neural networks to predict these cognitive labels on tens of thousands of brain images. Overcoming the heterogeneity, imbalance and noise in the training data, we successfully decoded more than 50 classes of mental processes on a large test set. This success demonstrates that image-based meta-analyses can be undertaken at scale and with minimal manual data curation. It enables broad reverse inferences, that is, concluding on mental processes given the observed brain activity.
Spinning ice floes reveal intensification of mesoscale eddies in the western Arctic Ocean
Authors: Manucharyan Georgy E. , Lopez-Acosta Rosalinda , Wilhelmus Monica M. 
Published: April 2022

AbstractUnder-ice eddies are prevalent in the major circulation system in the western Arctic Ocean, the Beaufort Gyre. Theoretical studies hypothesize that the eddy-driven overturning and the ice-ocean drag are crucial mechanisms of the gyre equilibration in response to atmospheric winds. However, due to severe weather conditions and limitations of remote sensing instruments, there are only sparse eddy observations in the ice-covered Arctic Ocean. Hence, the evolution of the under-ice eddy field, its impact on the gyre variability, and their mutual response to the ongoing Arctic warming remain uncertain. Here, we infer the characteristics of the under-ice eddy field by establishing its tight connection to the angular velocities of isolated spinning sea ice floes in marginal ice zones. Using over two decades of satellite observations of marginal ice zones in the western Arctic Ocean, we identified and tracked thousands of floes and used idealized eddy modeling to infer the interannual evolution of the eddy energetics underneath the ice. We find that the eddy field is strongly correlated to the strength of the Beaufort Gyre on interannual timescales, which provides the major observational evidence consistent with the hypothesis of the gyre equilibration by eddies. The inferred trends over the past two decades signify that the gyre and its eddy field have been intensifying as the sea ice cover has been declining. Our results imply that with continuing sea ice decline, the eddy field and the Beaufort Gyre will keep intensifying and leading to enhanced transport of freshwater and biogeochemical tracers.
Organocatalytic activity of granaticin and its involvement in bactericidal function
Authors: Nishiyama Tatsuya , Enomoto Narumi , Nagayasu Reina , Ueda Kenji 
Published: April 2022

AbstractWe previously discovered that actinorhodin, a benzoisochromanequinone antibiotic produced by Streptomyces coelicolor A3(2), serves as a catalyst facilitating the oxidation of ascorbic acid and cysteine (PNAS 48:17,152, 2014). In the present study, we screened for similar ascorbic acid-oxidizing activity in the culture broth of various Streptomyces spp., and discovered marked activity in the culture broth of Streptomyces vietnamensis. The principle active compound was granaticin, a pigmented antibiotic that is structurally related to actinorhodin. The absence of any metals in the purified granaticin fraction indicated that granaticin was an organocatalyst. Granaticin catalyzed the oxidation of L-ascorbic acid, generating L-dehydroascorbic acid and hydrogen peroxide (H2O2) at a 1:1 stoichiometric ratio, with 15 times higher reactivity than that of actinorhodin at an optimum pH of 7.0. Granaticin also oxidizes sulfhydryl compounds, including L-cysteine and glutathione. Growth inhibitory assays demonstrated that knockout mutants of the catalase gene exhibit high sensitivity to granaticin. The results suggest that the bactericidal activity of granaticin is exerted by the oxidation of sulfhydryl groups of cellular components and the toxicity of H2O2 generated during the oxidation reaction.
Postural control during turn on the light task assisted by functional electrical stimulation in post stroke subjects
Authors: Sousa Andreia S. P. , Moreira Juliana , Silva Claudia , Mesquita Inês , Silva Augusta , Macedo Rui , Santos Rubim 
Published: April 2022

AbstractPostural control mechanisms have a determinant role in reaching tasks and are typically impaired in post-stroke patients. Functional electrical stimulation (FES) has been demonstrated to be a promising therapy for improving upper limb (UL) function. However, according to our knowledge, no study has evaluated FES influence on postural control. This study aims to evaluate the influence of FES UL assistance, during turning on the light task, in the related postural control mechanisms. An observational study involving ten post-stroke subjects with UL dysfunction was performed. Early and anticipatory postural adjustments (EPAs and APAs, respectively), the weight shift, the center of pressure and the center of mass (CoM) displacement were analyzed during the turning on the light task with and without the FES assistance. FES parameters were adjusted to improve UL function according to a consensus between physiotherapists’ and patients’ perspectives. The ANOVA repeated measures, Paired sample t and McNemar tests were used to compare postural control between the assisted and non-assisted conditions. When the task was assisted by FES, the number of participants that presented APAs increased (p = 0.031). UL FES assistance during turning on the light task can improve postural control in neurological patients with UL impairments.
Ontogeny and caudal autotomy fracture planes in a large scincid lizard, Egernia kingii
Authors: Barr James I. , Boisvert Catherine A. , Trinajstic Kate , Bateman Philip W. 
Published: April 2022

AbstractMany lizard species use caudal autotomy, the ability to self-amputate a portion of the tail, as an effective but costly survival strategy. However, as a lizard grows, its increased size may reduce predation risk allowing for less costly strategies (e.g., biting and clawing) to be used as the primary defence. The King’s skink (Egernia kingii) is a large scincid up to approximately 244 mm snout to vent length (SVL) in size when adult. Adults rely less on caudal autotomy than do juveniles due to their size and strength increase during maturation. It has been hypothesised that lower behavioural reliance on autotomy in adults is reflected in loss or restriction of caudal vertebrae fracture planes through ossification as caudal intra-vertebral fracture planes in some species ossify during ontogenetic growth. To test this, we used micro-CT to image the tails of a growth series of seven individuals of E. kingii. We show that fracture planes are not lost or restricted ontogenetically within E. kingii, with adults retaining between 39–44 autotomisable vertebrae following 5–6 non-autotomisable vertebrae. Even though mature E. kingii rely less on caudal autotomy than do juveniles, this research shows that they retain the maximum ability to autotomise their tails, providing a last resort option to avoid threats. The potential costs associated with retaining caudal autotomy are most likely mitigated through neurological control of autotomy and E. kingii’s longevity.
sTREM-1 promotes the phagocytic function of microglia to induce hippocampus damage via the PI3K–AKT signaling pathway
Authors: Lu Li , Liu Xuan , Fu Juanhua , Liang Jun , Hou Yayi , Dou Huan 
Published: April 2022

AbstractSoluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a soluble form of TREM-1 released during inflammation. Elevated sTREM-1 levels have been found in neuropsychiatric systemic lupus erythematosus (NPSLE) patients; yet, the exact mechanisms remain unclear. This study investigated the role of sTREM-1 in brain damage and its underlying mechanism. The sTREM-1 recombinant protein (2.5 μg/3 μL) was injected into the lateral ventricle of C57BL/6 female mice. After intracerebroventricular (ICV) injection, the damage in hippocampal neurons increased, and the loss of neuronal synapses and activation of microglia increased compared to the control mice (treated with saline). In vitro. after sTREM-1 stimulation, the apoptosis of BV2 cells decreased, the polarization of BV2 cells shifted to the M1 phenotype, the phagocytic function of BV2 cells significantly improved, while the PI3K–AKT signal pathway was activated in vivo and in vitro. PI3K–AKT pathway inhibitor LY294002 reversed the excessive activation and phagocytosis of microglia caused by sTREM-1 in vivo and in vitro, which in turn improved the hippocampus damage. These results indicated that sTREM-1 activated the microglial by the PI3K–AKT signal pathway, and promoted its excessive phagocytosis of the neuronal synapse, thus inducing hippocampal damage. sTREM-1 might be a potential target for inducing brain lesions.
Burden of polycystic ovary syndrome in the Middle East and North Africa region, 1990–2019
Authors: Motlagh Asghari Kimia , Nejadghaderi Seyed Aria , Alizadeh Mahasti , Sanaie Sarvin , Sullman Mark J. M. , Kolahi Ali-Asghar , Avery Jodie , Safiri Saeid 
Published: April 2022

AbstractPolycystic ovary syndrome (PCOS) is one of the most important contributing factors to infertility. In this study, we report the burden of PCOS by age and sociodemographic index (SDI) for the 21 countries in the Middle East and North Africa (MENA) region. Publicly available data on the point prevalence, incidence and years lived with disability (YLDs), from 1990 to 2019, were retrieved from the Global Burden of Disease (GBD) 2019 study for the 21 countries in MENA. The results are presented with age-standardised numbers and rates per 100,000 population, along with their corresponding 95% uncertainty intervals (UIs). In 2019, the age-standardised point prevalence and incidence rate for PCOS in the MENA region were 2079.7 (95% UI: 1392.0 to 2812.3) and 77.2 (95% UI: 51.6 to 105.4) per 100,000, respectively, which represents a 37.9% (95% UI: 31.7 to 45.0) and a 33.7% (95% UI: 27.7 to 40.3) increase since 1990, respectively. Also in 2019, the age-standardised YLD rate of PCOS in this region was 18.7 (95% UI: 7.8 to 37.9) per 100,000 women, which has increased by 36.1% (95% UI: 29.4 to 43.4) since 1990. Kuwait [25.4 (10.7, 51.2)] had the highest age-standardised YLD rate, while Afghanistan [10.8 (10.1, 49.2)] had the lowest. Moreover, the largest increase in the YLD rate, from 1990 to 2019, was seen in Sudan [90.3% (64.1, 120.9)], whereas no country decreased during the measurement period. The total prevalent number and point prevalence of PCOS (per 100,000) were both highest in the 20–24 age group. The prevalence of PCOS was highest among women of reproductive age, but decreased rapidly after 45 years of age. Moreover, at the country level there was a positive association between SDI and the age-standardised YLD rates of PCOS. The growing prevalence and burden of PCOS in the MENA region highlights the need to implement cost-effective preventive programs, especially for women in their third decade of life, and in MENA countries with higher SDI levels.