bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-related differences in the effect of chronic alcohol on cognition and the brain: a systematic review
Authors: Kuhns Lauren , Kroon Emese , Lesscher Heidi , Mies Gabry , Cousijn Janna 
Published: August 2022

AbstractAdolescence is an important developmental period associated with increased risk for excessive alcohol use, but also high rates of recovery from alcohol use-related problems, suggesting potential resilience to long-term effects compared to adults. The aim of this systematic review is to evaluate the current evidence for a moderating role of age on the impact of chronic alcohol exposure on the brain and cognition. We searched Medline, PsycInfo, and Cochrane Library databases up to February 3, 2021. All human and animal studies that directly tested whether the relationship between chronic alcohol exposure and neurocognitive outcomes differs between adolescents and adults were included. Study characteristics and results of age-related analyses were extracted into reference tables and results were separately narratively synthesized for each cognitive and brain-related outcome. The evidence strength for age-related differences varies across outcomes. Human evidence is largely missing, but animal research provides limited but consistent evidence of heightened adolescent sensitivity to chronic alcohol’s effects on several outcomes, including conditioned aversion, dopaminergic transmission in reward-related regions, neurodegeneration, and neurogenesis. At the same time, there is limited evidence for adolescent resilience to chronic alcohol-induced impairments in the domain of cognitive flexibility, warranting future studies investigating the potential mechanisms underlying adolescent risk and resilience to the effects of alcohol. The available evidence from mostly animal studies indicates adolescents are both more vulnerable and potentially more resilient to chronic alcohol effects on specific brain and cognitive outcomes. More human research directly comparing adolescents and adults is needed despite the methodological constraints. Parallel translational animal models can aid in the causal interpretation of observed effects. To improve their translational value, future animal studies should aim to use voluntary self-administration paradigms and incorporate individual differences and environmental context to better model human drinking behavior.
The role of BDNF in mediating the prophylactic effects of (R,S)-ketamine on fear generalization and extinction
Authors: Ryan James D. , Tse Nathaniel , Huang Chienchun , Yang Ruirong , Lee Francis S. 
Published: August 2022

AbstractFear generalization is a conserved survival mechanism that can become maladaptive in the face of traumatic situations, a feature central to certain anxiety disorders including posttraumatic stress disorder (PTSD). However, the neural circuitry and molecular mechanisms underlying fear generalization remain unclear. Recent studies have shown that prophylactic treatment with (R,S)-ketamine confers protective effects in stress-induced depressive behaviors and enhances contextual fear discrimination, but the extent to which these effects extend to fear generalization after auditory fear conditioning remains unclear. Here, we build on this work by using a behavioral model of fear generalization in mice involving foot shocks with differential intensity levels during auditory fear conditioning. We find that prophylactic (R,S)-ketamine treatment exerts protective effects that results in enhanced fear discrimination in wild type mice. As the growth factor, brain-derived neurotrophic factor (BDNF), has been shown to mediate the rapid antidepressant actions of (R,S)-ketamine, we used a loss-of-function BDNF mouse line (BDNF Val66Met) to determine whether BDNF is involved in (R,S)-ketamine’s prophylactic effects on fear generalization. We found that BDNF Val66Met mice were resistant to the protective effects of prophylactic (R,S)-ketamine administration on fear generalization and extinction. We then used fiber photometry to parse out underlying neural activity and found that in the ventral hippocampus there were significant fear generalization-dependent patterns of activity for wild type and BDNF Val66Met mice that were altered by prophylactic (R,S)-ketamine treatment. Overall, these findings indicate a role for the ventral hippocampus and BDNF signaling in modulating the mitigating effects of prophylactic (R,S)-ketamine treatment on generalized fear.
Regulation of neuroendocrine plasticity by the RNA-binding protein ZFP36L1
Authors: Chen Hsiao-Yun , Durmaz Yavuz T. , Li Yixiang , Sabet Amin H. , Vajdi Amir , Denize Thomas , Walton Emily , Laimon Yasmin Nabil , Doench John G. , Mahadevan Navin R. , Losman Julie-Aurore , Barbie David A. , Tolstorukov Michael Y. , Rudin Charles M. , Sen Triparna , Signoretti Sabina , Oser Matthew G. 
Published: August 2022

AbstractSome small cell lung cancers (SCLCs) are highly sensitive to inhibitors of the histone demethylase LSD1. LSD1 inhibitors are thought to induce their anti-proliferative effects by blocking neuroendocrine differentiation, but the mechanisms by which LSD1 controls the SCLC neuroendocrine phenotype are not well understood. To identify genes required for LSD1 inhibitor sensitivity in SCLC, we performed a positive selection genome-wide CRISPR/Cas9 loss of function screen and found that ZFP36L1, an mRNA-binding protein that destabilizes mRNAs, is required for LSD1 inhibitor sensitivity. LSD1 binds and represses ZFP36L1 and upon LSD1 inhibition, ZFP36L1 expression is restored, which is sufficient to block the SCLC neuroendocrine differentiation phenotype and induce a non-neuroendocrine “inflammatory” phenotype. Mechanistically, ZFP36L1 binds and destabilizes SOX2 and INSM1 mRNAs, two transcription factors that are required for SCLC neuroendocrine differentiation. This work identifies ZFP36L1 as an LSD1 target gene that controls the SCLC neuroendocrine phenotype and demonstrates that modulating mRNA stability of lineage transcription factors controls neuroendocrine to non-neuroendocrine plasticity.
Epithelial-mesenchymal plasticity determines estrogen receptor positive breast cancer dormancy and epithelial reconversion drives recurrence
Authors: Aouad Patrick , Zhang Yueyun , De Martino Fabio , Stibolt Céline , Ali Simak , Ambrosini Giovanna , Mani Sendurai A. , Maggs Kelly , Quinn Hazel M. , Sflomos George , Brisken Cathrin 
Published: August 2022

AbstractMore than 70% of human breast cancers (BCs) are estrogen receptor α-positive (ER+). A clinical challenge of ER+BC is that they can recur decades after initial treatments. Mechanisms governing latent disease remain elusive due to lack of adequate in vivo models. We compare intraductal xenografts of ER+and triple-negative (TN) BC cells and demonstrate that disseminated TNBC cells proliferate similarly as TNBC cells at the primary site whereas disseminated ER+BC cells proliferate slower, they decreaseCDH1and increaseZEB1,2expressions, and exhibit characteristics of epithelial-mesenchymal plasticity (EMP) and dormancy. Forced E-cadherin expression overcomes ER+BC dormancy. Cytokine signalings are enriched in more activeversusinactive disseminated tumour cells, suggesting microenvironmental triggers for awakening. We conclude that intraductal xenografts model ER + BC dormancy and reveal that EMP is essential for the generation of a dormant cell state and that targeting exit from EMP has therapeutic potential.
Nanoscale segregation of channel and barrier claudins enables paracellular ion flux
Authors: Gonschior Hannes , Schmied Christopher , Van der Veen Rozemarijn Eva , Eichhorst Jenny , Himmerkus Nina , Piontek Jörg , Günzel Dorothee , Bleich Markus , Furuse Mikio , Haucke Volker , Lehmann Martin 
Published: August 2022

AbstractThe paracellular passage of ions and small molecules across epithelia is controlled by tight junctions, complex meshworks of claudin polymers that form tight seals between neighboring cells. How the nanoscale architecture of tight junction meshworks enables paracellular passage of specific ions or small molecules without compromising barrier function is unknown. Here we combine super-resolution stimulated emission depletion microscopy in live and fixed cells and tissues, multivariate classification of super-resolution images and fluorescence resonance energy transfer to reveal the nanoscale organization of tight junctions formed by mammalian claudins. We show that only a subset of claudins can assemble into characteristic homotypic meshworks, whereas tight junctions formed by multiple claudins display nanoscale organization principles of intermixing, integration, induction, segregation, and exclusion of strand assemblies. Interestingly, channel-forming claudins are spatially segregated from barrier-forming claudins via determinants mainly encoded in their extracellular domains also known to harbor mutations leading to human diseases. Electrophysiological analysis of claudins in epithelial cells suggests that nanoscale segregation of distinct channel-forming claudins enables barrier function combined with specific paracellular ion flux across tight junctions.
Microengineered devices enable long-term imaging of the ventral nerve cord in behaving adult Drosophila
Authors: Hermans Laura , Kaynak Murat , Braun Jonas , Ríos Victor Lobato , Chen Chin-Lin , Friedberg Adam , Günel Semih , Aymanns Florian , Sakar Mahmut Selman , Ramdya Pavan 
Published: August 2022

AbstractThe dynamics and connectivity of neural circuits continuously change on timescales ranging from milliseconds to an animal’s lifetime. Therefore, to understand biological networks, minimally invasive methods are required to repeatedly record them in behaving animals. Here we describe a suite of devices that enable long-term optical recordings of the adult Drosophila melanogaster ventral nerve cord (VNC). These consist of transparent, numbered windows to replace thoracic exoskeleton, compliant implants to displace internal organs, a precision arm to assist implantation, and a hinged stage to repeatedly tether flies. To validate and illustrate our toolkit we (i) show minimal impact on animal behavior and survival, (ii) follow the degradation of chordotonal organ mechanosensory nerve terminals over weeks after leg amputation, and (iii) uncover waves of neural activity caffeine ingestion. Thus, our long-term imaging toolkit opens up the investigation of premotor and motor circuit adaptations in response to injury, drug ingestion, aging, learning, and disease.
Consistent predator-prey biomass scaling in complex food webs
Authors: Perkins Daniel M. , Hatton Ian A. , Gauzens Benoit , Barnes Andrew D. , Ott David , Rosenbaum Benjamin , Vinagre Catarina , Brose Ulrich 
Published: August 2022

AbstractThe ratio of predator-to-prey biomass is a key element of trophic structure that is typically investigated from a food chain perspective, ignoring channels of energy transfer (e.g. omnivory) that may govern community structure. Here, we address this shortcoming by characterising the biomass structure of 141 freshwater, marine and terrestrial food webs, spanning a broad gradient in community biomass. We test whether sub-linear scaling between predator and prey biomass (a potential signal of density-dependent processes) emerges within ecosystem types and across levels of biological organisation. We find a consistent, sub-linear scaling pattern whereby predator biomass scales with the total biomass of their prey with a near ¾-power exponent within food webs - i.e. more prey biomass supports proportionally less predator biomass. Across food webs, a similar sub-linear scaling pattern emerges between total predator biomass and the combined biomass of all prey within a food web. These general patterns in trophic structure are compatible with a systematic form of density dependence that holds among complex feeding interactions across levels of organization, irrespective of ecosystem type.
Inducible expression of large gRNA arrays for multiplexed CRISPRai applications
Authors: Shaw William M. , Studená Lucie , Roy Kyler , Hapeta Piotr , McCarty Nicholas S. , Graham Alicia E. , Ellis Tom , Ledesma-Amaro Rodrigo 
Published: August 2022

AbstractCRISPR gene activation and inhibition (CRISPRai) has become a powerful synthetic tool for influencing the expression of native genes for foundational studies, cellular reprograming, and metabolic engineering. Here we develop a method for near leak-free, inducible expression of a polycistronic array containing up to 24 gRNAs from two orthogonal CRISPR/Cas systems to increase CRISPRai multiplexing capacity and target gene flexibility. To achieve strong inducibility, we create a technology to silence gRNA expression within the array in the absence of the inducer, since we found that long gRNA arrays for CRISPRai can express themselves even without promoter. Using this method, we create a highly tuned and easy-to-use CRISPRai toolkit in the industrially relevant yeast, Saccharomyces cerevisiae, establishing the first system to combine simultaneous activation and repression, large multiplexing capacity, and inducibility. We demonstrate this toolkit by targeting 11 genes in central metabolism in a single transformation, achieving a 45-fold increase in succinic acid, which could be precisely controlled in an inducible manner. Our method offers a highly effective way to regulate genes and rewire metabolism in yeast, with principles of gRNA array construction and inducibility that should extend to other chassis organisms.
Destabilisation of the Subpolar North Atlantic prior to the Little Ice Age
Authors: Arellano-Nava Beatriz , Halloran Paul R. , Boulton Chris A. , Scourse James , Butler Paul G. , Reynolds David J. , Lenton Timothy M. 
Published: August 2022

AbstractThe cooling transition into the Little Ice Age was the last notable shift in the climate system prior to anthropogenic global warming. It is hypothesised that sea-ice to ocean feedbacks sustained an initial cooling into the Little Ice Age by weakening the subpolar gyre circulation; a system that has been proposed to exhibit bistability. Empirical evidence for bistability within this transition has however been lacking. Using statistical indicators of resilience in three annually-resolved bivalve proxy records from the North Icelandic shelf, we show that the subpolar North Atlantic climate system destabilised during two episodes prior to the Little Ice Age. This loss of resilience indicates reduced attraction to one stable state, and a system vulnerable to an abrupt transition. The two episodes preceded wider subpolar North Atlantic change, consistent with subpolar gyre destabilisation and the approach of a tipping point, potentially heralding the transition to Little Ice Age conditions.
Electrocatalytic synthesis of adipic acid coupled with H2 production enhanced by a ligand modification strategy
Authors: Li Zhenhua , Li Xiaofan , Zhou Hua , Xu Yan , Xu Si-Min , Ren Yue , Yan Yifan , Yang Jiangrong , Ji Kaiyue , Li Li , Xu Ming , Shao Mingfei , Kong Xianggui , Sun Xiaoming , Duan Haohong 
Published: August 2022

AbstractAdipic acid is an important building block of polymers, and is commercially produced by thermo-catalytic oxidation of ketone-alcohol oil (a mixture of cyclohexanol and cyclohexanone). However, this process heavily relies on the use of corrosive nitric acid while releases nitrous oxide as a potent greenhouse gas. Herein, we report an electrocatalytic strategy for the oxidation of cyclohexanone to adipic acid coupled with H2 production over a nickel hydroxide (Ni(OH)2) catalyst modified with sodium dodecyl sulfonate (SDS). The intercalated SDS facilitates the enrichment of immiscible cyclohexanone in aqueous medium, thus achieving 3.6-fold greater productivity of adipic acid and higher faradaic efficiency (FE) compared with pure Ni(OH)2 (93% versus 56%). This strategy is demonstrated effective for a variety of immiscible aldehydes and ketones in aqueous solution. Furthermore, we design a realistic two-electrode flow electrolyzer for electrooxidation of cyclohexanone coupling with H2 production, attaining adipic acid productivity of 4.7 mmol coupled with H2 productivity of 8.0 L at 0.8 A (corresponding to 30 mA cm−2) in 24 h.
Flexible organic integrated electronics for self-powered multiplexed ocular monitoring
Authors: Lin Baojun , Wang Meng , Zhao Chao , Wang Shijie , Chen Kai , Li Xiao , Long Zaishang , Zhao Chenxu , Song Xinyue , Yan Sen , Wang Laili , Ma Wei 
Published: August 2022

AbstractSmart contact lens has drawn extensive research interests due to the noninvasive real-time detection of the human body to provide biomedical information for health management. However, it has been difficult to accurately measure the physiological signals in tears, and the use of external power source has also hindered the future applications. Here, we demonstrated an organic electrochemical transistor based multiplexed sensors self-powered by the organic solar cells (OSCs). The integrated device was fabricated via simple process including solution blade-coating and thermal evaporation. OSCs were optimized to provide optimal operation voltage for the sensors that exhibit semilog-linear response to the glucose and calcium ions in tear fluids without any peripheral circuits. The sensing signals can be transmitted to the laptop wirelessly through a near filed communication unit. This integrated self-powered multiplexed sensing device will provide real-time monitoring of the biomarkers in tears, prospected to be installed on the smart contact lens for the early detection and diagnosis of diabetes.
Comparison of risk factors for Parkinson’s disease, coronary events and ischemic stroke
Authors: Song Lu , Zhang Shunming , Li Huiping , Hansson Oskar , Sonestedt Emily , Borné Yan 
Published: August 2022

AbstractParkinson’s disease (PD) and cardiovascular disease share many important risk factors, but some associations differ. However, there are no studies that have compared their shared and specific risk factors. The present study aimed to compare risk factors for PD, coronary events, or ischemic stroke. We prospectively analyzed data from 26,210 participants with lifestyle factors aged 45–73 years enrolled between 1991 and 1996. The Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of PD, coronary events, or ischemic stroke in relation to each factor. A modified Lunn-McNeil competing risk analysis was performed to compare the HR strength of the three outcomes. A total of 486 incident PD cases, 3288 coronary events cases and 2,972 ischemic stroke cases occurred during a mean follow-up of 21 years. In multivariable models, age (per additional year: HR = 1.08; 95% CI: 1.06, 1.09), diabetes (HR = 1.52; 95% CI: 1.02, 2.26), neutrophil–lymphocyte ratio (per SD increase: HR = 1.09; 95% CI: 1.00, 1.19), and fasting blood glucose (per SD increase: HR = 1.18; 95% CI: 1.03, 1.36) are the risk factors for PD, whereas female sex (HR = 0.54; 95% CI: 0.43, 0.67), smoking (current smoker [HR = 0.57; 95% CI: 0.43, 0.74] and former smoker [HR = 0.81; 95% CI: 0.66, 0.99]), HDL (per SD increase: HR = 0.74; 95% CI: 0.57, 0.95), and LDL (per SD increase: HR = 0.77; 95% CI: 0.61, 0.96) are the protective factors. A comparison of risk factors for PD, coronary events, and ischemic stroke showed the three outcomes had concordant and discordant risk factors. Our results indicated the risk factor profiles for PD, coronary events, or ischemic stroke had many similarities, but also significant differences.
Synergistic effect of hydration and carbonation of ladle furnace aslag on cementitious substances
Authors: Yi Yuanrong , Ma Wenqing , Sidike Ainiwaer , Ma Zhongle , Fang Minghang , Lin Yue , Bai Shuqi , Chen Yinguang 
Published: August 2022

AbstractLadle furnace slag (LFS) can undergo hydration and carbonation reactions as cement. This article explores the effect of LFS hydration and carbonation reactions on cementitious substances at different temperatures and different LFS particle sizes, determining the effect of these varying conditions on the microstructure and formation mechanism of cementitious substances. The results show that in the early stages, C2S and C3S undergo hydration to generate C–S–H gel, which then undergoes decalcification and condensation to generate CaCO3 and Ca-deficient C–S–H gel; the hydration reaction and carbonation reaction promote and influence each other. The increase in temperature was found to hinder the formation of CaCO3 from Ca2+ and CO32−, thus reducing the efficiency of hydration carbonation. The increase in particle size was not conducive to the leaching of C2S and C3S to the surface of the reaction phase, which in turn reduced the degree of decalcification and polymerization of the C–S–H gel in the carbonation phase. It was concluded that the optimum LFS hydration and carbonation reactions were achieved at 20 °C and with a LFS particle sizes < 38 μm.
Regulation of MMP9 transcription by ETS1 in immortalized salivary gland epithelial cells of patients with salivary hypofunction and primary Sjögren’s syndrome
Authors: Noll Braxton , Mougeot Farah Bahrani , Brennan Michael T. , Mougeot Jean-Luc C. 
Published: August 2022

AbstractPrimary Sjögren’s syndrome (pSS) patients exhibit enhanced degradation of the salivary epithelium initially through MMP9 overexpression. We assessed the expression of MMP9 and an associated transcription factor, ETS1, in primary salivary gland epithelial cells (SGECs) and investigated potential regulatory mechanism(s) in immortalized SGECs. SGECs and iSGECs were derived from pSS and/or xerostomic “sicca” patients. siRNA knockdown of ETS1 in iSGECs was performed to determine MMP9 mRNA (qRT-PCR) and protein expression (ELISA). ETS1 binding to MMP9 promoter was assessed by luciferase activity and binding confirmed by mutagenesis and ChIP. Effects of ETS1 overexpression on progenitor and Epithelial-Mesenchymal transition (EMT) associated markers were determined by Western blot. Expression of ETS1 and its phosphorylated form in iSGECs was determined by immunofluorescence microscopy. ETS1 and MMP9 were overexpressed in SGECs of pSS and non-pSS sicca patients with salivary gland lymphocytic infiltration compared to non-pSS sicca patients without infiltration. ETS1 siRNA knockdown reduced both MMP9 mRNA and protein levels. ETS1 overexpression affected the expression of EMT and progenitor cell markers. Lastly, ETS1 bound the MMP9 promoter within the DNA region of −296 bp to −339 bp. ETS1 may impair salivary function through direct transcriptional control of the MMP9 promoter. ETS1 upregulation may also affect other factors involved in repair of the dysfunctional pSS salivary epithelium.
Influence of a circular obstacle on the dynamics of stable spiral waves with straining
Authors: Jaiswal Devanand , Kalita Jiten C 
Published: August 2022

AbstractThe current study envisages to investigate numerically, probably for the first time, the combined effect of a circular obstacle and medium motion on the dynamics of a stable rotating spiral wave. A recently reconstructed spatially fourth and temporally second order accurate, implicit, unconditionally stable high order compact scheme has been employed to carry out simulations of the Oregonator model of excitable media. Apart from studying the effect of the stoichiometric parameter, we provide detailed comparison between the dynamics of spiral waves with and without the circular obstacles in the presence of straining effect. In the process, we also inspect the dynamics of rigidly rotating spiral waves without straining effect in presence of the circular obstacle. The presence of the obstacle was seen to trigger transition to non-periodic motion for a much lower strain rate.