bluuebunny/crossref_metadata_2025 huggingface dataset:
Substance and Internet use during the COVID-19 pandemic in China
Authors: Huang Qiuping , Chen Xinxin , Huang Shucai , Shao Tianli , Liao Zhenjiang , Lin Shuhong , Li Yifan , Qi Jing , Cai Yi , Shen Hongxian
Published: September 2021

The coronavirus disease 2019 (COVID-19) has adversely influenced human physical and mental health, including emotional disorders and addictions. This study examined substance and Internet use behavior and their associations with anxiety and depression during the COVID-19 pandemic. An online self-report questionnaire was administered to 2196 Chinese adults between February 17 and 29, 2020. The questionnaire contained the seven-item Generalized Anxiety Disorder Scale (GAD-7) and Patient Health Questionnaire (PHQ-9), questions on demographic information, and items about substance and Internet use characteristics. Our results revealed that males consumed less alcohol (p < 0.001) and areca-nut (p = 0.012) during the pandemic than before the pandemic. Age, gender, education status, and occupation significantly differed among increased substance users, regular substance users, and nonsubstance users. Time spent on the Internet was significantly longer during the pandemic (p < 0.001) and 72% of participants reported increased dependence on the Internet. Compared to regular Internet users, increased users were more likely to be younger and female. Multiple logistic regression analysis revealed that age <33 years (OR = 2.034,p < 0.001), increased substance use (OR = 3.439,p < 0.001), and increased Internet use (OR = 1.914,p < 0.001) were significantly associated with depression. Moreover, anxiety was significantly related to female gender (OR = 2.065,p < 0.001), “unmarried” status (OR = 1.480,p = 0.017), nonstudents (OR = 1.946–3.030,p = 0.001), and increased substance use (OR = 4.291,p < 0.001). Although there was a significant decrease in social substance use during the pandemic, more attention should be paid to increased Internet use. Increased Internet use was significantly associated with both anxiety and depression, and increased substance use was related to depression. Professional support should be provided to vulnerable individuals to prevent addiction.
SAP130 released by damaged tubule drives necroinflammation via miRNA-219c/Mincle signaling in acute kidney injury
Authors: Lv Lin-Li , Wang Cui , Li Zuo-Lin , Cao Jing-Yuan , Zhong Xin , Feng Ye , Chen Jun , Tang Tao-Tao , Ni Hai-Feng , Wu Qiu-Li , Wang Bin , Lan Hui-Yao , Liu Bi-Cheng
Published: September 2021

Tubules injury and immune cell activation are the common pathogenic mechanisms in acute kidney injury (AKI). However, the exact modes of immune cell activation following tubule damage are not fully understood. Here we uncovered that the release of cytoplasmic spliceosome associated protein 130 (SAP130) from the damaged tubular cells mediated necroinflammation by triggering macrophage activation via miRNA-219c(miR-219c)/Mincle-dependent mechanism in unilateral ureteral obstruction (UUO) and cisplatin-induced AKI mouse models, and in patients with acute tubule necrosis (ATN). In the AKI kidneys, we found that Mincle expression was tightly correlated to the necrotic tubular epithelial cells (TECs) with higher expression of SAP130, a damaged associated molecule pattern (DAMP), suggesting that SAP130 released from damaged tubular cells may trigger macrophage activation and necroinflammation. This was confirmed in vivo in which administration of SAP130-rich supernatant from dead TECs or recombinant SAP130 promoted Mincle expression and macrophage accumulation which became worsen with profound tubulointerstitial inflammation in LPS-primed Mincle WT mice but not in Mincle deficient mice. Further studies identified that Mincle was negatively regulated via miR-219c-3p in macrophages as miR-219c-3p bound Mincle 3′-UTR to inhibit Mincle translation. Besides, lentivirus-mediated renal miR-219c-3p overexpression blunted Mincle and proinflammatory cytokine expression as well as macrophage infiltration in the inflamed kidney of UUO mice. In conclusion, SAP130 is released by damaged tubules which elicit Mincle activation on macrophages and renal necroinflammation via the miR-219c-3p-dependent mechanism. Results from this study suggest that targeting miR-219c-3p/Mincle signaling may represent a novel therapy for AKI.
Electrode pooling can boost the yield of extracellular recordings with switchable silicon probes
Authors: Lee Kyu Hyun , Ni Yu-Li , Colonell Jennifer , Karsh Bill , Putzeys Jan , Pachitariu Marius , Harris Timothy D. , Meister Markus
Published: September 2021

State-of-the-art silicon probes for electrical recording from neurons have thousands of recording sites. However, due to volume limitations there are typically many fewer wires carrying signals off the probe, which restricts the number of channels that can be recorded simultaneously. To overcome this fundamental constraint, we propose a method called electrode pooling that uses a single wire to serve many recording sites through a set of controllable switches. Here we present the framework behind this method and an experimental strategy to support it. We then demonstrate its feasibility by implementing electrode pooling on the Neuropixels 1.0 electrode array and characterizing its effect on signal and noise. Finally we use simulations to explore the conditions under which electrode pooling saves wires without compromising the content of the recordings. We make recommendations on the design of future devices to take advantage of this strategy.
Spin-valley coupling in single-electron bilayer graphene quantum dots
Authors: Banszerus L. , Möller S. , Steiner C. , Icking E. , Trellenkamp S. , Lentz F. , Watanabe K. , Taniguchi T. , Volk C. , Stampfer C.
Published: September 2021

Understanding how the electron spin is coupled to orbital degrees of freedom, such as a valley degree of freedom in solid-state systems, is central to applications in spin-based electronics and quantum computation. Recent developments in the preparation of electrostatically-confined quantum dots in gapped bilayer graphene (BLG) enable to study the low-energy single-electron spectra in BLG quantum dots, which is crucial for potential spin and spin-valley qubit operations. Here, we present the observation of the spin-valley coupling in bilayer graphene quantum dots in the single-electron regime. By making use of highly-tunable double quantum dot devices we achieve an energy resolution allowing us to resolve the lifting of the fourfold spin and valley degeneracy by a Kane-Mele type spin-orbit coupling of ≈ 60 μeV. Furthermore, we find an upper limit of a potentially disorder-induced mixing of the $$K$$
K
and $$K^{\prime}$$

K

′

states below 20 μeV.
Proposal for a continuous wave laser with linewidth well below the standard quantum limit
Authors: Liu Chenxu , Mucci Maria , Cao Xi , Dutt M. V. Gurudev , Hatridge Michael , Pekker David
Published: September 2021

Due to their high coherence, lasers are ubiquitous tools in science. We show that by engineering the coupling between the gain medium and the laser cavity as well as the laser cavity and the output port, it is possible to eliminate most of the noise due to photons entering as well as leaving the laser cavity. Hence, it is possible to reduce the laser linewidth by a factor equal to the number of photons in the laser cavity below the standard quantum limit. We design and theoretically analyze a superconducting circuit that uses Josephson junctions, capacitors and inductors to implement a microwave laser, including the low-noise couplers that allow the design to surpass the standard quantum limit. Our proposal relies on the elements of superconducting quantum information, and thus is an example of how quantum engineering techniques can inspire us to re-imagine the limits of conventional quantum systems.
Deep learning framework for material design space exploration using active transfer learning and data augmentation
Authors: Kim Yongtae , Kim Youngsoo , Yang Charles , Park Kundo , Gu Grace X. , Ryu Seunghwa
Published: September 2021

Neural network-based generative models have been actively investigated as an inverse design method for finding novel materials in a vast design space. However, the applicability of conventional generative models is limited because they cannot access data outside the range of training sets. Advanced generative models that were devised to overcome the limitation also suffer from the weak predictive power on the unseen domain. In this study, we propose a deep neural network-based forward design approach that enables an efficient search for superior materials far beyond the domain of the initial training set. This approach compensates for the weak predictive power of neural networks on an unseen domain through gradual updates of the neural network with active transfer learning and data augmentation methods. We demonstrate the potential of our framework with a grid composite optimization problem that has an astronomical number of possible design configurations. Results show that our proposed framework can provide excellent designs close to the global optima, even with the addition of a very small dataset corresponding to less than 0.5% of the initial training dataset size.
Nanosilica modified with polyaspartic acid as an industrial circulating water scale inhibitor
Authors: Cheng Yamin , Guo Xinyu , Zhao Xiaowei , Wu Yufeng , Cao Zhongyan , Cai Yonghong , Xu Ying
Published: September 2021

Given the special performance of nanosilica with its small size, large specific surface area and high surface activity, nanosilica containing reactive amino group (denoted as SiO2–NH2) and polysuccinimide were allowed to take part in polymerization reaction to afford SiO2–NH2 modified polyaspartic acid (denoted as SiO2–NH2/PASP), a potential polymer scale inhibitor with good water solubility for industrial circulating water. The scale inhibition performance of the as-prepared SiO2–NH2/PASP was evaluated by static scale inhibition test; and its scale inhibition mechanism was explored by means of scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. Results indicated that SiO2–NH2/PASP exhibits excellent scale inhibition performance against CaSO4 and CaCO3 at very low concentrations (optimum scale inhibition rate of 100% and 68%, respectively), and the presence of 5 mg/L of SiO2–NH2/PASP greatly increases the inhibition efficiency of CaSO4 and CaCO3 scale by 21% and 53%, obviously higher than that of pure PASP.
Optical read-out of Coulomb staircases in a moiré superlattice via trapped interlayer trions
Authors: Baek Hyeonjun , Brotons-Gisbert Mauro , Campbell Aidan , Vitale Valerio , Lischner Johannes , Watanabe Kenji , Taniguchi Takashi , Gerardot Brian D.
Published: September 2021

Moiré patterns with a superlattice potential can be formed by vertically stacking two layered materials with a relative twist or lattice constant mismatch. In transition metal dichalcogenide-based systems, the moiré potential landscape can trap interlayer excitons (IXs) at specific atomic registries. Here, we report that spatially isolated trapped IXs in a molybdenum diselenide/tungsten diselenide heterobilayer device provide a sensitive optical probe of carrier filling in their immediate environment. By mapping the spatial positions of individual trapped IXs, we are able to spectrally track the emitters as the moiré lattice is filled with excess carriers. Upon initial doping of the heterobilayer, neutral trapped IXs form charged IXs (IX trions) uniformly with a binding energy of ~7 meV. Upon further doping, the empty superlattice sites sequentially fill, creating a Coulomb staircase: stepwise changes in the IX trion emission energy due to Coulomb interactions with carriers at nearest-neighbour moiré sites. This non-invasive, highly local technique can complement transport and non-local optical sensing techniques to characterize Coulomb interaction energies, visualize charge correlated states, or probe local disorder in a moiré superlattice.
Structures of outer-arm dynein array on microtubule doublet reveal a motor coordination mechanism
Authors: Rao Qinhui , Han Long , Wang Yue , Chai Pengxin , Kuo Yin-wei , Yang Renbin , Hu Fangheng , Yang Yuchen , Howard Jonathon , Zhang Kai
Published: September 2021

Thousands of outer-arm dyneins (OADs) are arrayed in the axoneme to drive a rhythmic ciliary beat. Coordination among multiple OADs is essential for generating mechanical forces to bend microtubule doublets (MTDs). Using electron microscopy, we determined high-resolution structures ofTetrahymena thermophilaOAD arrays bound to MTDs in two different states. OAD preferentially binds to MTD protofilaments with a pattern resembling the native tracks for its distinct microtubule-binding domains. Upon MTD binding, free OADs are induced to adopt a stable parallel conformation, primed for array formation. Extensive tail-to-head (TTH) interactions between OADs are observed, which need to be broken for ATP turnover by the dynein motor. We propose that OADs in an array sequentially hydrolyze ATP to slide the MTDs. ATP hydrolysis in turn relaxes the TTH interfaces to effect free nucleotide cycles of downstream OADs. These findings lead to a model explaining how conformational changes in the axoneme produce coordinated action of dyneins.
Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity
Authors: Cimino Irene , Rimmington Debra , Tung Y. C. Loraine , Lawler Katherine , Larraufie Pierre , Kay Richard G. , Virtue Samuel , Lam Brian Y. H. , Fagnocchi Luca , Ma Marcella K. L. , Saudek Vladimir , Zvetkova Ilona , Vidal-Puig Antonio , Yeo Giles S. H. , Farooqi I. Sadaf , Pospisilik J. Andrew , Gribble Fiona M. , Reimann Frank , O’Rahilly Stephen , Coll Anthony P.
Published: September 2021

Neuronatin (Nnat) has previously been reported to be part of a network of imprinted genes downstream of the chromatin regulator Trim28. Disruption of Trim28 or of members of this network, including neuronatin, results in an unusual phenotype of a bimodal body weight. To better characterise this variability, we examined the key contributors to energy balance in Nnat+/−p mice that carry a paternal null allele and do not express Nnat. Consistent with our previous studies, Nnat deficient mice on chow diet displayed a bimodal body weight phenotype with more than 30% of Nnat+/−p mice developing obesity. In response to both a 45% high fat diet and exposure to thermoneutrality (30 °C) Nnat deficient mice maintained the hypervariable body weight phenotype. Within a calorimetry system, food intake in Nnat+/−p mice was hypervariable, with some mice consuming more than twice the intake seen in wild type littermates. A hyperphagic response was also seen in Nnat+/−p mice in a second, non-home cage environment. An expected correlation between body weight and energy expenditure was seen, but corrections for the effects of positive energy balance and body weight greatly diminished the effect of neuronatin deficiency on energy expenditure. Male and female Nnat+/−p mice displayed subtle distinctions in the degree of variance body weight phenotype and food intake and further sexual dimorphism was reflected in different patterns of hypothalamic gene expression in Nnat+/−p mice. Loss of the imprinted gene Nnat is associated with a highly variable food intake, with the impact of this phenotype varying between genetically identical individuals.
Influence of TGFB1 and CTLA4 polymorphisms on calcineurin inhibitors dose and risk of acute rejection in renal transplantation
Authors: Bogacz Anna , Wolek Marlena , Sieńko Jerzy , Czerny Bogusław , Machaliński Bogusław , Olbromski Piotr , Kotowski Maciej
Published: September 2021

Organ transplant is often the treatment of choice as it extends and improves patient life. Immunosuppressive treatment, which prevents acute rejection of the organ, is used in transplant patients to prevent the loss of transplant. The aim of the study was to determine the impact of the CTLA4 (+49A>G, rs231775) and the TGF-β1 (−800G>A, rs1800468) polymorphisms on the therapeutic effect of immunosuppressive drugs (cyclosporine—CsA, tacrolimus—TAC) and the risk of acute rejection in renal transplant patients. The analysis of the CTLA4 +49A>G and the TGF-β1 −800G>A polymorphisms was carried out in 392 patients after kidney transplant using real-time PCR. The CTLA4 +49A>G polymorphism did not affect CsA or TAC dose, ratio of drug concentration to dose (C/D), and blood concentrations. As for the TGF-β1 -800G>A polymorphism, patients with the GA genotype required lower TAC doses compared to the GG genotype (TAC 12 h: 3.63 mg vs 5.3 mg, TAC 24 h: 2.38 mg vs 3.29 mg). Comparing the C/D ratio in both groups (TAC 12 h and TAC 24 h), higher C/D ratio was observed in patients with the GA genotype. These results indicate that patients with the A allele require slightly lower doses of TAC. The results suggest that the TGF-β1 −800 G>A polymorphism may influence the TAC dose, while the +49A>G polymorphism of the CTLA4 gene does not correlate with the dose of CsA or TAC. The analysis of the biochemical parameters of the renal profile showed no impact of the CTLA4 and the TGF-β1 polymorphisms on the risk of organ rejection.
Low-grade albuminuria in adult and elderly individuals with diabetes mellitus and arterial hypertension accompanied by Primary Health Care
Authors: de Resende Matheus Augusto Soares , Ferreira Emily de Souza , Dias Heloísa Helena , Santos Daniel Souza , Batistelli Clara Regina Santos , Borges Luiza Delazari , Comini Luma de Oliveira , Moreira Tiago Ricardo , da Costa Glauce Dias , da Silva Eunice Ferreira , da Silva Rodrigo Gomes , Cotta Rosângela Minardi Mitre
Published: September 2021

Diabetes mellitus (DM) and arterial hypertension (AH) are the two main clinical conditions related to Chronic Kidney Disease (CKD); disease also identify by the levels of low-grade albuminuria (LGA). Few studies have simultaneously investigated the associations of glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) with LGA. Our study aimed to investigate and compare the association of HbA1c and FPG with the probability of LGA in adult and elderly individuals with DM and AH, within the scope of Primary Health Care (PHC). Cross-sectional study involving 737 Brazilians individuals previously diagnosed with hypertension and/or diabetes. Tests for HbA1c, FPG and LGA were performed. LGA was defined as the highest quartile of albumin urinary (≥ 13 mg/g) among individuals with urinary LGA < 30 mg / g. A significant increase in the prevalence of LGA was found with increasing levels of HbA1c (p < 0.001). There was a significant association of HbA1c with LGA (p < 0.001) and increased probability of LGA for participants with HbA1c ≥ 6.5% compared to those with Hba1c < 5.7% (OR [95% CI]: 2.43 [1.32–4.46], p < 0.05), after adjusting for confounding factors, except when adjusted for FPG (p = 0.379 and p = 0.359, respectively). HbA1c and FPG were significantly associated in a collinear manner with an increased probability of LGA in adult and elderly individuals with DM and AH.
Extreme rainfall deficits were not the cause of recurring colonial era famines of southern Indian semi-arid regions
Authors: Ray Ranjini , Bhattacharya Atreyee , Arora Gaurav , Bajaj Kushank , Horton Keyle , Chen Shi , Chakraborty Supriyo , Bazaz Amir
Published: September 2021

Using information contained in the eighteenth to twentieth century British administrative documents, preserved in the National Archives of India (NAI), we present a 218-year (1729–1947 AD) record of socioeconomic disruptions and human impacts (famines) associated with ‘rain failures’ that affected the semi-arid regions (SARs) of southern India. By mapping the southern Indian famine record onto long-term spatiotemporal measures of regional rainfall variability, we demonstrate that the SARs of southern India repeatedly experienced famines when annual rainfall reduced by ~ one standard deviation (1 SD), or more, from long-term averages. In other words, ‘rain failures’ listed in the colonial documents as causes of extreme socioeconomic disruptions, food shortages and human distress (famines) in the southern Indian SARs were fluctuations in precipitation well within the normal range of regional rainfall variability and not extreme rainfall deficits (≥ 3 SD). Our study demonstrates that extreme climate events were not necessary conditions for extreme socioeconomic disruptions and human impacts rendered by the colonial era famines in peninsular India. Based on our findings, we suggest that climate change risk assessement should consider the potential impacts of more frequent low-level anomalies (e.g. 1 SD) in drought prone semi-arid regions.
Increased vulnerability to SARS-CoV-2 infection among indigenous people living in the urban area of Manaus
Authors: Pontes Gemilson Soares , de Melo Silva Jean , Pinheiro-Silva Renato , Barbosa Anderson Nogueira , Santos Luciano Cardenes , de Pádua Quirino Ramalho Antônio , de Castro Alves Carlos Eduardo , da Silva Danielle Furtado , de Oliveira Leonardo Calheiros , da Costa Allyson Guimarães , Bruno Ana Carla
Published: September 2021

The COVID-19 pandemic threatens indigenous peoples living in suburban areas of large Brazilian cities and has thus far intensified their pre-existing socio-economic inequalities. We evaluated the epidemiological situation of SARS-CoV-2 infection among residents of the biggest urban multiethnic indigenous community of the Amazonas state, Brazil. Blood samples of 280 indigenous people living in the surrounding area of Manaus were tested for the presence of anti-SARS-CoV-2 IgA or IgG antibodies. The risk factors and sociodemographic information were assessed through an epidemiological questionnaire. We found a total positivity rate of 64.64% (95% CI 59.01–70.28) for SARS-CoV-2 infection. IgA and IgG were detected in 55.71% (95% CI 49.89–61.54) and 60.71% (95% CI 54.98–66.45) of the individuals, respectively. Over 80% of positive individuals were positive for both IgA and IgG.No significant difference in positivity rates between genders or age groups was observed. Moreover, the age group ≥ 60 years old showed the highest antibody ratios (IgA mean ratio = 3.080 ± 1.623; IgG mean ratio = 4.221 ± 1.832), while the age groups 13–19 and 20–29 showed the lowest IgA (mean ratio = 2.268 ± 0.919) and IgG ratios (mean ratio = 2.207 ± 1.246), respectively. Individuals leaving the home more frequently were at higher risk of infection (Odds ratio (OD) 2.61; 95% CI 1.00–1.49; p = 0.048). Five or more individuals per household increased fivefold the risk of virus transmission (OR 2.56; 95% CI 1.09–6.01; p = 0.019). The disproportionate dissemination of SARS-CoV-2 infection observed among the study population might be driven by typical cultural behavior and socioeconomic inequalities. Despite the pandemic threat, this population is not being targeted by public policies and appears to be chronically invisible to the Brazilian authorities.
Screening and predicting progression from high-risk mild cognitive impairment to Alzheimer’s disease
Authors: Ge Xiao-Yan , Cui Kai , Liu Long , Qin Yao , Cui Jing , Han Hong-Juan , Luo Yan-Hong , Yu Hong-Mei
Published: September 2021

Individuals with mild cognitive impairment (MCI) are clinically heterogeneous, with different risks of progression to Alzheimer’s disease. Regular follow-up and examination may be time-consuming and costly, especially for MRI and PET. Therefore, it is necessary to identify a more precise MRI population. In this study, a two-stage screening frame was proposed for evaluating the predictive utility of additional MRI measurements among high-risk MCI subjects. In the first stage, the K-means cluster was performed for trajectory-template based on two clinical assessments. In the second stage, high-risk individuals were filtered out and imputed into prognosis models with varying strategies. As a result, the ADAS-13 was more sensitive for filtering out high-risk individuals among patients with MCI. The optimal model included a change rate of clinical assessments and three neuroimaging measurements and was significantly associated with a net reclassification improvement (NRI) of 0.246 (95% CI 0.021, 0.848) and integrated discrimination improvement (IDI) of 0.090 (95% CI − 0.062, 0.170). The ADAS-13 longitudinal models had the best discrimination performance (Optimism-corrected concordance index = 0.830), as validated by the bootstrap method. Considering the limited medical and financial resources, our findings recommend follow-up MRI examination 1 year after identification for high-risk individuals, while regular clinical assessments for low-risk individuals.
Simulation and estimation of future ecological risk on the Qinghai-Tibet Plateau
Authors: Wang Shengzhen , Liu Fenggui , Zhou Qiang , Chen Qiong , Liu Fei
Published: September 2021

Over the past 50 years, temperatures on the Qinghai-Tibet Plateau (QTP) have risen roughly twice as fast as the global average, making it the most unpredictable region of environmental change due to global warming. In this paper, an Environmental Area Index model was developed using data from the Coupled Model Intercomparison Project to assess the ecological risk faced by QTP ecosystems under the influence of climate factors. The results show that ecological risk gradually decreases from northwest to the southeast, and there are different trends in ecological risk for each class in areas with different elevation gradients. As elevation increased, the proportion of potential risk areas gradually decreased, and the proportion of high- and higher-risk areas gradually increased. We predict that in the period 2021–2100, the overall ecological risk change trend on the QTP will not be obvious, but there will be a more obvious change on the vertical gradient. In general, under the existing global climate change scenario, the ecological risk faced by the QTP show a decreasing trend under the influence of climate factors, and the decrease in ecological risks is much higher at higher elevations than at lower elevations.
Understanding physical drivers of the 2015/16 marine heatwaves in the Northwest Atlantic
Authors: Perez E. , Ryan S. , Andres M. , Gawarkiewicz G. , Ummenhofer C. C. , Bane J. , Haines S.
Published: September 2021

The Northwest Atlantic, which has exhibited evidence of accelerated warming compared to the global ocean, also experienced several notable marine heatwaves (MHWs) over the last decade. We analyze spatiotemporal patterns of surface and subsurface temperature structure across the Northwest Atlantic continental shelf and slope to assess the influences of atmospheric and oceanic processes on ocean temperatures. Here we focus on MHWs from 2015/16 and examine their physical drivers using observational and reanalysis products. We find that a combination of jet stream latitudinal position and ocean advection, mainly due to warm core rings shed by the Gulf Stream, plays a role in MHW development. While both atmospheric and oceanic drivers can lead to MHWs they have different temperature signatures with each affecting the vertical structure differently and horizontal spatial patterns of a MHW. Northwest Atlantic MHWs have significant socio-economic impacts and affect commercially important species such as squid and lobster.
Serum inflammatory profiles in cystic fibrosis mice with and without Bordetella pseudohinzii infection
Authors: Litman Paul M. , Day Alexander , Kelley Thomas J. , Darrah Rebecca J.
Published: September 2021

Cystic fibrosis (CF) is an autosomal recessive disease caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein, and is marked by an accumulation of mucus in affected airways resulting in persistent infection and chronic inflammation. Quantitative differences in inflammatory markers have been observed in CF patient serum, tracheal cells, and bronchoalveolar lavage fluid, in the absence of detectable infection, implying that absent CFTR function alone may result in dysregulated immune responses. To examine the relationship between absent CFTR and systemic inflammation, 22 analytes were measured in CF mice (F508del/F508del) sera using the MSD multiplex platform. Pro-inflammatory cytokines IL-2, TNF-α, IL-17α, IFN-γ, IL-1β, and MIP-3α are significantly elevated in infection-naïve CF mice (p < 0.050). Anti-inflammatory cytokines IL-10 and IL-4 are also significantly increased (p = 0.00003, p = 0.004). Additionally, six general markers of inflammation are significantly different from non-CF controls (p < 0.050). To elucidate the effects of chronic infection on the CF inflammatory profile, we examined CF mice exposed to spontaneous Bordetella pseudohinzii infections. There are no statistical differences in nearly all inflammatory markers when compared to their infection-naïve CF counterparts, except in the Th2-derived IL-4 and IL-5 which demonstrate significant decreases following exposure (p = 0.046, p = 0.045). Lastly, following acute infection, CF mice demonstrate elevations in nearly all inflammatory markers, but exhibit a shortened return to uninfected levels over time, and suppression of Th1-derived IL-2 and IL-5 (p = 0.043, p = 0.011). These results imply that CF mice have a persistent inflammatory profile often indistinguishable from chronic infection, and a dysregulated humoral response during and following active infection.
Fear-specific leftward bias in gaze direction judgment
Authors: Zhang Yue , Hu Qiqi , Lai Xinwei , Hu Zhonghua , Gao Shan
Published: September 2021

Previous studies have shown that humans have a left spatial attention bias in cognition and behaviour. However, whether there exists a leftward perception bias of gaze direction has not been investigated. To address this gap, we conducted three behavioural experiments using a forced-choice gaze direction judgment task. The point of subjective equality (PSE) was employed to measure whether there was a leftward perception bias of gaze direction, and if there was, whether this bias was modulated by face emotion. The results of experiment 1 showed that the PSE of fearful faces was significantly positive as compared to zero and this effect was not found in angry, happy, and neutral faces, indicating that participants were more likely to judge the gaze direction of fearful faces as directed to their left-side space, namely a leftward perception bias. With the response keys counterbalanced between participants, experiment 2a replicated the findings in experiment 1. To further investigate whether the gaze direction perception variation was contributed by emotional or low-level features of faces, experiment 2b and 3 used inverted faces and inverted eyes, respectively. The results revealed similar leftward perception biases of gaze direction in all types of faces, indicating that gaze direction perception was biased by emotional information in faces rather than low-level facial features. Overall, our study demonstrates that there a fear-specific leftward perception bias in processing gaze direction. These findings shed new light on the cerebral lateralization in humans.
A prelude to the proximity interaction mapping of CXXC5
Authors: Ayaz Gamze , Turan Gizem , Olgun Çağla Ece , Kars Gizem , Karakaya Burcu , Yavuz Kerim , Demiralay Öykü Deniz , Can Tolga , Muyan Mesut , Yaşar Pelin
Published: September 2021

CXXC5 is a member of the zinc-finger CXXC family proteins that interact with unmodified CpG dinucleotides through a conserved ZF-CXXC domain. CXXC5 is involved in the modulation of gene expressions that lead to alterations in diverse cellular events. However, the underlying mechanism of CXXC5-modulated gene expressions remains unclear. Proteins perform their functions in a network of proteins whose identities and amounts change spatiotemporally in response to various stimuli in a lineage-specific manner. Since CXXC5 lacks an intrinsic transcription regulatory function or enzymatic activity but is a DNA binder, CXXC5 by interacting with proteins could act as a scaffold to establish a chromatin state restrictive or permissive for transcription. To initially address this, we utilized the proximity-dependent biotinylation approach. Proximity interaction partners of CXXC5 include DNA and chromatin modifiers, transcription factors/co-regulators, and RNA processors. Of these, CXXC5 through its CXXC domain interacted with EMD, MAZ, and MeCP2. Furthermore, an interplay between CXXC5 and MeCP2 was critical for a subset of CXXC5 target gene expressions. It appears that CXXC5 may act as a nucleation factor in modulating gene expressions. Providing a prelude for CXXC5 actions, our results could also contribute to a better understanding of CXXC5-mediated cellular processes in physiology and pathophysiology.
New nematogenic conical-shaped supramolecular H-bonded complexes for solar energy investigations
Authors: Gomha Sobhi M. , Ahmed Hoda A. , Shaban Mohamed , Abolibda Tariq Z. , Alharbi Khalid Abdulaziz , Alalawy Hafsa H.
Published: September 2021

New conical-shaped geometrical supramolecular H-bonded liquid crystal complexes were formed through 1:2 intermolecular interactions of H-bonding between flexible core (adipic acid,A) and lateral chloro-substituted azopyridines (Bn). The chains of the terminally alkoxy substituted base (n) were changed between 8 and 16 carbons. Mesomorphic and optical examinations of the prepared complexes were measured via differential scanning calorimetry (DSC) and polarizing optical microscopy (POM). Fourier-transform infrared spectroscopy (FT-IR) was used to confirm the Fermi bands of the H- bonding interactions. Induced nematogenic mesophases that cover the whole lengths of alkoxy-chains were detected. The non-linear geometries of the designed supramolecular complexes were also confirmed via Density functional theory (DFT) calculations. It was found that the length of terminal alkoxy chain of the base moiety highly affects the geometrical structure of the investigated complexes. Moreover, it increases the thermodynamic energy and influences the geometrical parameters. The electrical properties of each of the acid component (A), the base (B16) and their 1:2 complex (A/2B16) were evaluated using the Keithley measurement-source unit. The optical properties studies showed that the influences in the optical absorption and the reduction of the energy gap of the complex compared to its individual components made the resulted supramolecular H-bonded complex soft material suitable for solar energy investigations.
Overexpression of wild-type human amyloid precursor protein alters GABAergic transmission
Authors: Kreis Anna , Desloovere Jana , Suelves Nuria , Pierrot Nathalie , Yerna Xavier , Issa Farah , Schakman Olivier , Gualdani Roberta , de Clippele Marie , Tajeddine Nicolas , Kienlen-Campard Pascal , Raedt Robrecht , Octave Jean-Noël , Gailly Philippe
Published: September 2021

The function of the amyloid precursor protein (APP) is not fully understood, but its cleavage product amyloid beta (Aβ) together with neurofibrillary tangles constitute the hallmarks of Alzheimer’s disease (AD). Yet, imbalance of excitatory and inhibitory neurotransmission accompanied by loss of synaptic functions, has been reported much earlier and independent of any detectable pathological markers. Recently, soluble APP fragments have been shown to bind to presynaptic GABAB receptors (GABABRs), subsequently decreasing the probability of neurotransmitter release. In this body of work, we were able to show that overexpression of wild-type human APP in mice (hAPPwt) causes early cognitive impairment, neuronal loss, and electrophysiological abnormalities in the absence of amyloid plaques and at very low levels of Aβ. hAPPwt mice exhibited neuronal overexcitation that was evident in EEG and increased long-term potentiation (LTP). Overexpression of hAPPwt did not alter GABAergic/glutamatergic receptor components or GABA production ability. Nonetheless, we detected a decrease of GABA but not glutamate that could be linked to soluble APP fragments, acting on presynaptic GABABRs and subsequently reducing GABA release. By using a specific presynaptic GABABR antagonist, we were able to rescue hyperexcitation in hAPPwt animals. Our results provide evidence that APP plays a crucial role in regulating inhibitory neurotransmission.
The emerging vertebrate model species for neurophysiological studies is Danionella cerebrum, new species (Teleostei: Cyprinidae)
Authors: Britz Ralf , Conway Kevin W. , Rüber Lukas
Published: September 2021

The four described species of Danionella are tiny, transparent fishes that mature at sizes between 10–15 mm, and represent some of the most extreme cases of vertebrate progenesis known to date. The miniature adult size and larval appearance of Danionella, combined with a diverse behavioral repertoire linked to sound production by males, have established Danionella as an important model for neurophysiological studies. The external similarity between the different species of Danionella has offered an important challenge to taxonomic identification using traditional external characters, leading to confusion over the identity of the model species. Using combined morphological and molecular taxonomic approaches, we show here that the most extensively studied species of Danionella is not D. translucida, but represents an undescribed species, D. cerebrum n. sp. that is externally almost identical to D. translucida, but differs trenchantly in several internal characters. Molecular analyses confirm the distinctiveness of D. cerebrum and D. translucida and suggest that the two species are not even sister taxa. Analysis of the evolution of sexual dimorphisms associated with the Weberian apparatus reveals significant increases in complexity from the simpler condition found in D. dracula, to most complex conditions in D. cerebrum, D. mirifica and D. translucida.
Non-invasively measured brain activity and radiological progression in diffuse glioma
Authors: Numan T. , Kulik S. D. , Moraal B. , Reijneveld J. C. , Stam C. J. , de Witt Hamer P. C. , Derks J. , Bruynzeel A. M. E. , van Linde M. E. , Wesseling P. , Kouwenhoven M. C. M. , Klein M. , Würdinger T. , Barkhof F. , Geurts J. J. G. , Hillebrand A. , Douw L.
Published: September 2021

Non-invasively measured brain activity is related to progression-free survival in glioma patients, suggesting its potential as a marker of glioma progression. We therefore assessed the relationship between brain activity and increasing tumor volumes on routine clinical magnetic resonance imaging (MRI) in glioma patients. Postoperative magnetoencephalography (MEG) was recorded in 45 diffuse glioma patients. Brain activity was estimated using three measures (absolute broadband power, offset and slope) calculated at three spatial levels: global average, averaged across the peritumoral areas, and averaged across the homologues of these peritumoral areas in the contralateral hemisphere. Tumors were segmented on MRI. Changes in tumor volume between the two scans surrounding the MEG were calculated and correlated with brain activity. Brain activity was compared between patient groups classified into having increasing or stable tumor volume. Results show that brain activity was significantly increased in the tumor hemisphere in general, and in peritumoral regions specifically. However, none of the measures and spatial levels of brain activity correlated with changes in tumor volume, nor did they differ between patients with increasing versus stable tumor volumes. Longitudinal studies in more homogeneous subgroups of glioma patients are necessary to further explore the clinical potential of non-invasively measured brain activity.
Minimally-invasive insertion strategy and in vivo evaluation of multi-shank flexible intracortical probes
Authors: Srikantharajah Kagithiri , Medinaceli Quintela Renata , Doerenkamp Kerstin , Kampa Björn M. , Musall Simon , Rothermel Markus , Offenhäusser Andreas
Published: September 2021

Chronically implanted neural probes are powerful tools to decode brain activity however, recording population and spiking activity over long periods remains a major challenge. Here, we designed and fabricated flexible intracortical Michigan-style arrays with a shank cross-section per electrode of 250 μm$$^2$$

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utilizing the polymer paryleneC with the goal to improve the immune acceptance. As flexible neural probes are unable to penetrate the brain due to the low buckling force threshold, a tissue-friendly insertion system was developed by reducing the effective shank length. The insertion strategy enabled the implantation of the four, bare, flexible shanks up to 2 mm into the mouse brain without increasing the implantation footprint and therefore, minimizing the acute trauma. In acute recordings from the mouse somatosensory cortex and the olfactory bulb, we demonstrated that the flexible probes were able to simultaneously detect local field potentials as well as single and multi-unit activity. Additionally, the flexible arrays outperformed stiff probes with respect to yield of single unit activity. Following the successful in vivo validation, we further improved the microfabrication towards a double-metal-layer process, and were able to double the number of electrodes per shank by keeping the shank width resulting in a cross-section per electrode of 118 μm$$^2$$

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Delusional thinking and action binding in healthy individuals
Authors: Cao Liyu , Steinborn Michael B. , Haendel Barbara F.
Published: September 2021

Action binding is the effect that the perceived time of an action is shifted towards the action related feedback. A much larger action binding effect in schizophrenia compared to normal controls has been shown, which might be due to positive symptoms like delusions. Here we investigated the relationship between delusional thinking and action binding in healthy individuals, predicting a positive correlation between them. The action binding effect was evaluated by comparing the perceived time of a keypress between an operant (keypress triggering a sound) and a baseline condition (keypress alone), with a novel testing method that massively improved the precision of the subjective timing measurement. A positive correlation was found between the tendency of delusional thinking (measured by the 21-item Peters et al. delusions inventory) and action binding across participants after controlling for the effect of testing order between operant and baseline conditions. The results indicate that delusional thinking in particular influences action time perception and support the notion of a continuous distribution of schizotypal traits with normal controls at one end and clinical patients at the other end.
Distance-based clustering challenges for unbiased benchmarking studies
Authors: Thrun Michael C.
Published: September 2021

Benchmark datasets with predefined cluster structures and high-dimensional biomedical datasets outline the challenges of cluster analysis: clustering algorithms are limited in their clustering ability in the presence of clusters defining distance-based structures resulting in a biased clustering solution. Data sets might not have cluster structures. Clustering yields arbitrary labels and often depends on the trial, leading to varying results. Moreover, recent research indicated that all partition comparison measures can yield the same results for different clustering solutions. Consequently, algorithm selection and parameter optimization by unsupervised quality measures (QM) are always biased and misleading. Only if the predefined structures happen to meet the particular clustering criterion and QM, can the clusters be recovered. Results are presented based on 41 open-source algorithms which are particularly useful in biomedical scenarios. Furthermore, comparative analysis with mirrored density plots provides a significantly more detailed benchmark than that with the typically used box plots or violin plots.
Prepulse inhibition predicts subjective hearing in rats
Authors: Wake Naoki , Ishizu Kotaro , Abe Taiki , Takahashi Hirokazu
Published: September 2021

Auditory studies in animals benefit from quick and accurate audiometry. The auditory brainstem response (ABR) and prepulse inhibition (PPI) have been widely used for hearing assessment in animals, but how well these assessments predict subjective audiometry still remains unclear. Human studies suggest that subjective audiometry is consistent with the ABR-based audiogram, not with the PPI-based audiogram, likely due to top-down processing in the cortex that inhibits PPI. Here, we challenged this view in Wistar rats, as rodents exhibit less complexity of cortical activities and thereby less influence of the cerebral cortex on PPI compared to humans. To test our hypothesis, we investigated whether subjective audiometry correlates with ABR- or PPI-based audiograms across the range of audible frequencies in Wistar rats. The subjective audiogram was obtained through pure-tone audiometry based on operant conditioning. Our results demonstrated that both the ABR-based and PPI-based audiograms significantly correlated to the subjective audiogram. We also found that ASR strength was information-rich, and adequate interpolation of this data offered accurate audiometry. Thus, unlike in humans, PPI could be used to predict subjective audibility in rats.
Atrial high-rate episodes predict major adverse cardio/cerebrovascular events in patients with cardiac implantable electrical devices
Authors: Chen Ju-Yi , Chen Tse-Wei , Lu Wei-Da
Published: September 2021

Patients with atrial high-rate episodes (AHRE) have a high risk of neurologic events, although the causal role and optimal cutoff threshold of AHRE for major adverse cardio/cerebrovascular events (MACCE) are unknown. This study aimed to identify independent factors for AHRE and subsequent atrial fibrillation (AF) after documented AHRE. We enrolled 470 consecutive patients undergoing cardiac implantable electrical device (CIED) implantations. The primary endpoint was subsequent MACCE after AHRE ≥ 6 min, 6 h, and 24 h. AHRE was defined as > 175 beats per minute (bpm) (Medtronic®) or > 200 bpm (Biotronik®) lasting ≥ 30 s. Multivariate Cox regression analysis with time-dependent covariates was used to determine variables associated with independent risk of MACCE. The patients’ median age was 76 year, and 126 patients (26.8%) developed AHRE ≥ 6 min, 63 (13.4%) ≥ 6 h, and 39 (8.3%) ≥ 24 h. During follow-up (median: 29 months), 142 MACCE occurred in 123 patients. Optimal AHRE cutoff value was 6 min, with highest Youden index for MACCE. AHRE ≥ 6 min ~ 24 h was independently associated with MACCE and predicted subsequent AF. Male gender, lower body mass index, or BMI, and left atrial diameter were independently associated with AHRE ≥ 6 min ~ 24 h. Patients with CIEDs who develop AHRE ≥ 6 min have an independently increased risk of MACCE. Comprehensive assessment of patients with CIEDs is warranted.
Auditory hallucinations activate language and verbal short-term memory, but not auditory, brain regions
Authors: Fuentes-Claramonte Paola , Soler-Vidal Joan , Salgado-Pineda Pilar , García-León María Ángeles , Ramiro Nuria , Santo-Angles Aniol , Llanos Torres María , Tristany Josep , Guerrero-Pedraza Amalia , Munuera Josep , Sarró Salvador , Salvador Raymond , Hinzen Wolfram , McKenna Peter J. , Pomarol-Clotet Edith
Published: September 2021

Auditory verbal hallucinations (AVH, ‘hearing voices’) are an important symptom of schizophrenia but their biological basis is not well understood. One longstanding approach proposes that they are perceptual in nature, specifically that they reflect spontaneous abnormal neuronal activity in the auditory cortex, perhaps with additional ‘top down’ cognitive influences. Functional imaging studies employing the symptom capture technique—where activity when patients experience AVH is compared to times when they do not—have had mixed findings as to whether the auditory cortex is activated. Here, using a novel variant of the symptom capture technique, we show that the experience of AVH does not induce auditory cortex activation, even while real speech does, something that effectively rules out all theories that propose a perceptual component to AVH. Instead, we find that the experience of AVH activates language regions and/or regions that are engaged during verbal short-term memory.