Miracle-dz/UniFAR-FTUs huggingface dataset:
Close Homolog of L1 Regulates Dendritic Spine Density in the Mouse Cerebral Cortex Through Semaphorin 3B

Dendritic spines in the developing mammalian neocortex are initially overproduced and then eliminated during adolescence to achieve appropriate levels of excitation in mature networks. We show here that the L1 family cell adhesion molecule Close Homolog of L1 (CHL1) and secreted repellent ligand Semaphorin 3B (Sema3B) function together to induce dendritic spine pruning in developing cortical pyramidal neurons. Loss of CHL1 in null mutant mice in both genders resulted in increased spine density and a greater proportion of immature spines on apical dendrites in the prefrontal and visual cortex. Electron microscopy showed that excitatory spine synapses with postsynaptic densities were increased in the CHL1-null cortex, and electrophysiological recording in prefrontal slices from mutant mice revealed deficiencies in excitatory synaptic transmission. Mechanistically, Sema3B protein induced elimination of spines on apical dendrites of cortical neurons cultured from wild-type but not CHL1-null embryos. Sema3B was secreted by the cortical neuron cultures, and its levels increased when cells were treated with the GABA antagonist gabazine. In vivo CHL1 was coexpressed with Sema3B in pyramidal neuron subpopulations and formed a complex with Sema3B receptor subunits Neuropilin-2 and PlexinA4. CHL1 and NrCAM, a closely related L1 adhesion molecule, localized primarily to distinct spines and promoted spine elimination to Sema3B or Sema3F, respectively. These results support a new concept in which selective spine elimination is achieved through different secreted semaphorins and L1 family adhesion molecules to sculpt functional neural circuits during postnatal maturation. SIGNIFICANCE STATEMENT Dendritic spines in the mammalian neocortex are initially overproduced and then pruned in adolescent life through unclear mechanisms to sculpt maturing cortical circuits. Here, we show that spine and excitatory synapse density of pyramidal neurons in the developing neocortex is regulated by the L1 adhesion molecule, Close Homolog of L1 (CHL1). CHL1 mediated spine pruning in response to the secreted repellent ligand Semaphorin 3B and associated with receptor subunits Neuropilin-2 and PlexinA4. CHL1 and related L1 adhesion molecule NrCAM localized to distinct spines, and promoted spine elimination to Semaphorin 3B and -3F, respectively. These results support a new concept in which selective elimination of individual spines and nascent synapses can be achieved through the action of distinct secreted semaphorins and L1 adhesion molecules.
HCC-Derived Exosomes: Critical Player and Target for Cancer Immune Escape

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver, and currently the second most common cause of cancer-related deaths worldwide with increasing incidence and poor prognosis. Exosomes are now considered as important mediators of host anti-tumor immune response as well as tumor cell immune escape. HCC-derived exosomes have been shown to attenuate the cytotoxicity of T-cells and NK cells, and promote the immuno-suppressive M2 macrophages, N2 neutrophils, and Bregs. These exosomes harbor several immune-related non-coding RNAs and proteins that drive immune-escape and tumor progression, and thus may serve as potential diagnostic biomarkers and therapeutic targets for HCC. In a previous study, we identified miR146a as an exosomal factor that promotes M2-polarization and suppresses the anti-HCC function of T-cells. In this review, we summarized the role of tumor-derived exosomes and their key components in mediating tumor immune escape during HCC development.
Kainic acid Induces production and aggregation of amyloid β-protein and memory deficits by activating inflammasomes in NLRP3- and NF-κB-stimulated pathways

Kainic acid (KA) treatment causes neuronal degeneration, which is a feature of Alzheimer’s disease (AD) symptoms such as amyloid β-protein production and memory deficits. Inflammasomes are known to be critical for the progression of AD. However, the underlying mechanism by which inflammasomes influence AD progression remains unknown. The present study investigated the damaging effect of KA on neurons by focusing on the inflammasome-mediated signaling pathways. Assessments using cultured microglia and mouse brains demonstrated that KA treatment specifically induced inflammasome activation. Mechanistic evaluations showed that KA activated two major components of inflammasomes, nucleotide binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) and nuclear factor (NF)-κB, which resulted in the production of interleukin-1β (IL-1β) and brain-derived neurotrophic factor (BDNF). Inhibition of NLRP3 or NF-κB by Bay11-7082 caused a reduction in the KA-induced expression of interleukin (IL)-1β and BDNF. Moreover, knockdown of the expression of KA receptors (KARs) such as Grik1 and Grik3 induced suppression of NLRP3 and NF-κB, suggesting that KARs function upstream of NLRP3 and NF-κB to mediate the effects of KA on regulation of IL-1β and BDNF expression. Notably, IL-1β was shown to exert positive effects on the expression of BACE1, which is blocked by Bay11-7082. Overall, our results revealed that Bay11-7082 acts against KA-induced neuronal degeneration, amyloid β-protein (Aβ) deposition, and memory defects via inflammasomes and further highlighted the protective role of Bay11-7082 in KA-induced neuronal defects.
Association Between Transcatheter Aortic Valve Replacement for Bicuspid vs Tricuspid Aortic Stenosis and Mortality or Stroke.

Importance Transcatheter aortic valve replacement (TAVR) indications are expanding, leading to an increasing number of patients with bicuspid aortic stenosis undergoing TAVR. Pivotal randomized trials conducted to obtain US Food and Drug Administration approval excluded bicuspid anatomy. Objective To compare the outcomes of TAVR with a balloon-expandable valve for bicuspid vs tricuspid aortic stenosis. Design, Setting, and Participants Registry-based prospective cohort study of patients undergoing TAVR at 552 US centers. Participants were enrolled in the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapies Registry from June 2015 to November 2018. Exposures TAVR for bicuspid vs tricuspid aortic stenosis. Main Outcomes and Measures Primary outcomes were 30-day and 1-year mortality and stroke. Secondary outcomes included procedural complications, valve hemodynamics, and quality of life assessment. Results Of 81 822 consecutive patients with aortic stenosis (2726 bicuspid; 79 096 tricuspid), 2691 propensity-score matched pairs of bicuspid and tricuspid aortic stenosis were analyzed (median age, 74 years [interquartile range {IQR}, 66-81 years]; 39.1%, women; mean [SD] STS-predicted risk of mortality, 4.9% [4.0%] and 5.1% [4.2%], respectively). All-cause mortality was not significantly different between patients with bicuspid and tricuspid aortic stenosis at 30 days (2.6% vs 2.5%; hazard ratio [HR], 1.04, [95% CI, 0.74-1.47]) and 1 year (10.5% vs 12.0%; HR, 0.90 [95% CI, 0.73-1.10]). The 30-day stroke rate was significantly higher for bicuspid vs tricuspid aortic stenosis (2.5% vs 1.6%; HR, 1.57 [95% CI, 1.06-2.33]). The risk of procedural complications requiring open heart surgery was significantly higher in the bicuspid vs tricuspid cohort (0.9% vs 0.4%, respectively; absolute risk difference [RD], 0.5% [95% CI, 0%-0.9%]). There were no significant differences in valve hemodynamics. There were no significant differences in moderate or severe paravalvular leak at 30 days (2.0% vs 2.4%; absolute RD, 0.3% [95% CI, -1.3% to 0.7%]) and 1 year (3.2% vs 2.5%; absolute RD, 0.7% [95% CI, -1.3% to 2.7%]). At 1 year there was no significant difference in improvement in quality of life between the groups (difference in improvement in the Kansas City Cardiomyopathy Questionnaire overall summary score, -2.4 [95% CI, -5.1 to 0.3]; P = .08). Conclusions and Relevance In this preliminary, registry-based study of propensity-matched patients who had undergone transcatheter aortic valve replacement for aortic stenosis, patients with bicuspid vs tricuspid aortic stenosis had no significant difference in 30-day or 1-year mortality but had increased 30-day risk for stroke. Because of the potential for selection bias and the absence of a control group treated surgically for bicuspid stenosis, randomized trials are needed to adequately assess the efficacy and safety of transcatheter aortic valve replacement for bicuspid aortic stenosis.
Acoustically Driven Micromixing: Effect of Transducer Geometry

The ability to drive efficient micromixing on a microfluidic platform is crucial for a wide range of lab-on-a-chip applications. Here, we investigate the ability of acoustic waves generated on different geometric surfaces (concave and convex) to enhance the micromixing efficiency in droplet acoustomicrofluidic systems, and, concomitantly, to reduce the power consumption in these devices for a given performance requirement. Quite counterintuitively, we observe that although the acoustic streaming velocity, which scaled inversely with the droplet size, tended to be generally lower (by approximately 45%) when the flow is generated by transducers with convex surfaces compared to those with concave surfaces, the mixing efficiency is disproportionately higher: compared to pure diffusional mixing in the absence of the acoustic forcing, the mixing efficiency due to the acoustically driven convection increased by up to 25% and 43% on these respective surfaces. As such, the mixing enhancement cannot simply be attributed to an increase in the convective flow arising from the acoustic forcing. Rather, we observe the mixing enhancement to be due to the stronger chaotic advection arising in the transducer with the convex surface due to its diverging acoustic field into the droplet.
Herbicide Resistance Management: Recent Developments and Trends

This review covers recent developments and trends in herbicide-resistant (HR) weed management in agronomic field crops. In countries where input-intensive agriculture is practiced, these developments and trends over the past decade include renewed efforts by the agrichemical industry in herbicide discovery, cultivation of crops with combined (stacked) HR traits, increasing reliance on preemergence vs. postemergence herbicides, breeding for weed-competitive crop cultivars, expansion of harvest weed seed control practices, and advances in site-specific or precision weed management. The unifying framework or strategy underlying these developments and trends is mitigation of viable weed seeds into the soil seed bank and maintaining low weed seed banks to minimize population proliferation, evolution of resistance to additional herbicidal sites of action, and spread. A key question going forward is: how much weed control is enough to consistently achieve the goal of low weed seed banks? The vision for future HR weed management programs must be sustained crop production and profitability with reduced herbicide (particularly glyphosate) dependency.
Characterization of serum irisin in patients with severe acute pancreatitis

Background Irisin, as a novel and versatile hormone secreted by skeletal myocytes and fat tissues, is reported to be involved in inflammation-related diseases; one of the main characteristics of severe acute pancreatitis (SAP) is inflammatory responses. This study aims to describe the characteristics of irisin in SAP. Patients and methods Here, we enrolled 50 controls, 20 with no acute pancreatitis (AP), 20 AP, and 12 SAP patients, determined white blood cell, blood glucose, C-reactive protein, urine amylase, blood lipase, and serum irisin using an analyzer and enzyme-linked immunosorbent assay at the indicated time-points, analyzed the correlations of irisin with blood glucose, sex, and age, and then predicted the morality and complications of organ failure and/or exacerbations of comorbidities in SAP by irisin. Results The results showed no significant difference in all groups in the clinical parameters (P>0.05), except that white blood cell was significantly higher in no AP, AP, and SAP than the controls (P<0.05). In addition, irisin levels were significantly lower and maintained a steadily low trend in the process of SAP than others (P<0.05), whereas C-reactive protein, urine amylase, and blood lipase in the SAP and AP groups were higher than others and kept decreasing tendency (P<0.01). Moreover, the irisin level in female SAP patients was significantly higher than that in male patients, but no differences were found in the other groups (P>0.05). In addition, the correlation between irisin levels and blood glucose was better in the SAP group than that between irisin levels and age in SAP patients and controls, although a relatively better correlation was found in SAP patients than the controls. Finally, the prognostic significance of mortality and complications of SAP according to irisin levels represented significantly, especially for complications of organ failure and/or exacerbations of comorbidities in female SAP. Conclusion Therefore, serum irisin level has unique characteristics and may be an independent factor and useful to predict the mortality, and complications in SAP patients, especially in female SAP patients.
The Evolving Role of CD8+CD28− Immunosenescent T Cells in Cancer Immunology

Functional, tumor-specific CD8+ cytotoxic T lymphocytes drive the adaptive immune response to cancer. Thus, induction of their activity is the ultimate aim of all immunotherapies. Success of anti-tumor immunotherapy is precluded by marked immunosuppression in the tumor microenvironment (TME) leading to CD8+ effector T cell dysfunction. Among the many facets of CD8+ T cell dysfunction that have been recognized—tolerance, anergy, exhaustion, and senescence—CD8+ T cell senescence is incompletely understood. Naïve CD8+ T cells require three essential signals for activation, differentiation, and survival through T-cell receptor, costimulatory receptors, and cytokine receptors. Downregulation of costimulatory molecule CD28 is a hallmark of senescent T cells and increased CD8+CD28− senescent populations with heterogeneous roles have been observed in multiple solid and hematogenous tumors. T cell senescence can be induced by several factors including aging, telomere damage, tumor-associated stress, and regulatory T (Treg) cells. Tumor-induced T cell senescence is yet another mechanism that enables tumor cell resistance to immunotherapy. In this paper, we provide a comprehensive overview of CD8+CD28− senescent T cell population, their origin, their function in immunology and pathologic conditions, including TME and their implication for immunotherapy. Further characterization and investigation into this subset of CD8+ T cells could improve the efficacy of future anti-tumor immunotherapy.
Putative novel cps loci in a large global collection of pneumococci

The pneumococcus produces a polysaccharide capsule, encoded by the cps locus, that provides protection against phagocytosis and determines serotype. Nearly 100 serotypes have been identified with new serotypes still being discovered, especially in previously understudied regions. Here we present an analysis of the cps loci of more than 18 000 genomes from the Global Pneumococcal Sequencing (GPS) project with the aim of identifying novel cps loci with the potential to produce previously unrecognized capsule structures. Serotypes were assigned using whole genome sequence data and 66 of the approximately 100 known serotypes were included in the final dataset. Closer examination of each serotype’s sequences identified nine putative novel cps loci (9X, 11X, 16X, 18X1, 18X2, 18X3, 29X, 33X and 36X) found in ~2.6 % of the genomes. The large number and global distribution of GPS genomes provided an unprecedented opportunity to identify novel cps loci and consider their phylogenetic and geographical distribution. Nine putative novel cps loci were identified and examples of each will undergo subsequent structural and immunological analysis.
Moving Into the Loop: An Investigation of Drivers’ Steering Behavior in Highly Automated Vehicles

Objective This paper investigates driver engagement with vehicle automation and the transition to manual control in the context of a phenomenon that we have termed vicarious steering—drivers steering when the vehicle is under automated control. Background Automated vehicles introduce many challenges, including disengagement from the driving task and out-of-the-loop performance decrement. We examine drivers’ steering behavior when the automation is engaged, and steering input has no effect on the vehicle state. Such vicarious steering is a potential indicator of engagement for evaluating automated vehicles. Method A total of 32 female and 32 male drivers between 25 and 55 years of age participated in this experiment. A 2 × 2 between-subject design combined control algorithms and instructed responsibility. The control algorithms (lane centering and adaptive) were intended to convey the capability of the automation. The adaptive algorithm drifted across the lane center when latent hazards were present. The instructed levels of responsibility (driver primarily responsible and automation primarily responsible) were intended to replicate the admonitions of owners’ manuals. Results The adaptive algorithm increased vicarious steering (p < .001), but instructed responsibility did not (p = .67), and there was no interaction between the algorithm and the responsibility (p = .75). Vicarious steering was associated with an increase in transitions to manual control and glances to the road but was negatively associated with driving performance immediately after the transition to manual control. Conclusion Vicarious steering is a promising indicator of driver engagement when the vehicle is under automated control and automation algorithms can promote engagement.
An Integrated Analysis of Maternal-Infant Sleep, Breastfeeding, and Sudden Infant Death Syndrome Research Supporting a Balanced Discourse

Breastfeeding and the place of sleep for the mother and the infant have been controversial internationally due to reported concerns regarding infant deaths despite the known benefits of exclusive and prolonged breastfeeding, which are increased by breastfeeding at night. The aims of this integrated analysis were to (a) review breastfeeding and maternal and infant sleep research literature via historical, epidemiological, anthropological, and methodological lenses; (b) use this information to determine where we are currently in safeguarding both infant lives and breastfeeding; and (c) postulate the direction that research might take from this point forward to improve our knowledge and inform our policy and practice. Despite well-meaning but unsuccessful campaigns in some countries to dissuade parents from sleeping with their babies, many breastfeeding mothers and caregivers do sleep with their infants whether intentionally or unintentionally. Taking cultural contexts and socio-ecological circumstances into consideration, data supports policies to counsel parents and caregivers on safe sleep practices, including bed-sharing in non-hazardous circumstances, particularly in the absence of parental smoking, recent parental alcohol consumption, or sleeping next to an adult on a sofa. Further research with appropriate methodology is needed to drill down on actual rates of infant deaths, paying close attention to the definitions of deaths, the circumstances of the deaths, and confounding factors, in order to ensure we have the best information with which to derive public health policy. Introduction and use of the concept of “breastsleeping” is a plausible way to remove the negative connotations of “co-sleeping” and redirect ongoing data-driven discussions and education of best practices of breastfeeding and sleep.
Small RNA Functions as a Trafficking Effector in Plant Immunity

Small RNAs represent a class of small but powerful agents that regulate development and abiotic and biotic stress responses during plant adaptation to a constantly challenging environment. Previous findings have revealed the important roles of small RNAs in diverse cellular processes. The recent discovery of bidirectional trafficking of small RNAs between different kingdoms has raised many interesting questions. The subsequent demonstration of exosome-mediated small RNA export provided a possible tool for further investigating how plants use small RNAs as a weapon during the arms race between plant hosts and pathogens. This review will focus on discussing the roles of small RNAs in plant immunity in terms of three aspects: the biogenesis of extracellular small RNAs and the transportation and trafficking small RNA-mediated gene silencing in pathogens.
The Effects of Filter’s Class, Cutoff Frequencies, and Independent Component Analysis on the Amplitude of Somatosensory Evoked Potentials Recorded from Healthy Volunteers

Objective: The aim of this study was to investigate the effects of different preprocessing parameters on the amplitude of median nerve somatosensory evoked potentials (SEPs). Methods: Different combinations of two classes of filters (Finite Impulse Response (FIR) and Infinite Impulse Response (IIR)), three cutoff frequency bands (0.5–1000 Hz, 3–1000 Hz, and 30–1000 Hz), and independent component analysis (ICA) were used to preprocess SEPs recorded from 17 healthy volunteers who participated in two sessions of 1000 stimulations of the right median nerve. N30 amplitude was calculated from frontally placed electrode (F3). Results: The epochs classified as artifacts from SEPs filtered with FIR compared to those filtered with IIR were 1% more using automatic and 140% more using semi-automatic methods (both p < 0.001). There were no differences in N30 amplitudes between FIR and IIR filtered SEPs. The N30 amplitude was significantly lower for SEPs filtered with 30–1000 Hz compared to the bandpass frequencies 0.5–1000 Hz and 3–1000 Hz. The N30 amplitude was significantly reduced when SEPs were cleaned with ICA compared to the SEPs from which non-brain components were not removed using ICA. Conclusion: This study suggests that the preprocessing of SEPs should be done carefully and the neuroscience community should come to a consensus regarding SEP preprocessing guidelines, as the preprocessing parameters can affect the outcomes that may influence the interpretations of results, replicability, and comparison of different studies.
Efficient Fabrication Process of Ordered Metal Nanodot Arrays for Infrared Plasmonic Sensor

In this paper, a simple process to fabricate ordered Au nanodot arrays up to 520 nm in diameter that respond to infrared light is developed, and the feasibility of its application to infrared plasmonic sensors is shown. The developed process utilizes thermal dewetting to agglomerate a coated gold film into nanodots. It was difficult to produce large nanodots that responded to infrared light owing to dot separation. In this paper, therefore, the mechanism of dot agglomeration by thermal dewetting is studied via an experiment and theoretical model, and conditions to form single nanodots are clarified. Furthermore, Au nanodot arrays of 100 nm to 520 nm in diameter were fabricated by this process, and their absorption spectra were analyzed. In addition, an analysis of the change in the peak wavelength against the refractive index indicates the possibility of further improvement of the sensitivity of the infrared plasmon sensors.