bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous RNA and protein profiling using a TurboID proximity‐labeling strategy
Authors: Ramelow Christina C , Sunna Sydney N , Rayaprolu Sruti , Sampson Maureen , Seyfried Nicholas T. , Sloan Steven , Rangaraju Srikant 
Published: December 2021

AbstractBackgroundBiologically relevant insights into cellular disease mechanisms of neurons and glia can be obtained by complimentary molecular profiling of the transcriptome and proteome of these cells. While mutually exclusive pipelines are available, the information surveyed is often from different samples leading to poor correlation between the transcriptome and proteome. Our goal was to develop a method for concomitant cell type‐specific analyses of RNA and protein.MethodWe utilized a proximity‐labeling strategy that uses the biotin ligase, TurboID, to efficiently label the proteome, in a mouse microglial BV2 cell line. We created a stable BV2‐TurboID cell line that expresses TurboID fused to a nuclear export sequence. Biotin treatment of BV2‐TurboID cells resulted in robust biotinylation of the cellular proteome as confirmed by Western blot and by label‐free quantitation mass spectrometry (LFQ‐MS) of biotinylated proteins enriched with streptavidin beads. LFQ‐MS revealed that TurboID biotinylates several RNA‐binding proteins (RBPs) including ribosomal units, suggesting that transcripts associated with RBPs may also be pulled down simultaneously with proteins. To test this, we homogenized BV2‐Turbo and control BV2 cells, enriched biotinylated proteins with streptavidin beads while maintaining RNA‐protein interactions, and then eluted RNA.ResultQuality control studies showed negligible mRNA from streptavidin pulldowns from control BV2 cells, while BV2‐TurboID pulldowns had larger mRNA yields with high quality. NanoString neuroinflammatory profiling (800 genes) of whole cell RNA from control BV2 and BV2‐TurboID cells and streptavidin pulldowns from both cell types were performed. We observed a 23‐fold higher mRNA yield in the BV2‐TurboID pulldowns compared to control BV2 cells for 550 genes included in the analyses. Transcript abundances from total RNA and BV2‐TurboID pulldowns were highly comparable (R2=0.97; no differentially expressed genes) with equivalent abundance of microglial genes (e.g., Spp1 and Apoe) suggesting a faithful transcriptome capture.ConclusionOur novel TurboID proximity labeling approach can simultaneously capture cell type‐specific transcriptomes and proteomes. We are now validating this method in other cell types using RNA‐sequencing and MS approaches. Once validated, this concurrent RNA and protein profiling approach can be applied to in vivo and ex vivo model systems to investigate the distinct roles brain cell types play in development, aging, and disease.
CHOP is not a main contributor to tau‐mediated toxicity
Authors: Criado‐Marrero Marangelie , Blair Laura J. 
Published: December 2021

AbstractBackgroundIn Alzheimer's disease (AD), the accumulation of the microtubule associated protein tau is linked with neuronal loss, but the major cell death pathway remains to be identified. Pathogenic tau promotes endoplasmic reticulum (ER) stress and subsequent unfolded protein response (UPR) activation. However, the contribution of ER stress to tau‐mediated toxicity in neurons is unknown. A previous study demonstrated that mice lacking CHOP/Ddit3, an important regulator of ER stress‐induced cell death, were protected from ER stress induced neuronal loss. We hypothesized that silencing CHOP would prevent tau toxicity through the ER stress pathway and reveal the contribution of tau toxicity that is mediated through this pathway.MethodTo investigate this, we generated a mouse‐targeting CHOP/Ddit3 shRNA AAV9 that also expresses GFP by a separate promoter. We injected shCHOP AAV9 or a shScrambled control AAV9 in the brains of 8‐month‐old male and female rTg4510 tau transgenic mice and harvested them at 12‐months of age, when ER stress is activated, and neuronal loss is occurring in these mice. We performed behavioral studies using the Y‐Maze, Open field, and 2‐day Radial‐Arm water maze task with a reversal paradigm. Unbiased stereology was used to determine neuronal health and effect of CHOP shRNA on CHOP levels was evaluated by immunofluorescence.ResultAAV9 CHOP shRNA did not alter spatial learning and memory in tau transgenic mice. Evaluation of the tissue revealed a modest, but non‐significant increase in neuronal loss from CHOP knock down, while the DG shows a non‐significant decrease in neuronal loss. Tissue volume was unchanged in both regions. Very surprising to us, and opposite of what was expected, we found that in these regions of interest the CHOP levels increased in the animal expressing the CHOP.ConclusionOverall, this suggests that shCHOP AAV9 does not alter tau‐modified behaviors such as learning and memory particularly at this timepoint. Our results also suggest that there may be a compensatory increase in CHOP signaling in neighboring cells, suggesting that the activation of the UPR in the brains of these mice may be a protective mechanism.
Genome‐wide meta‐analysis of age‐related cognitive decline in population‐based older individuals
Authors: Acharya Vibha , Fan Kang‐Hsien , Snitz Beth E , Ganguli Mary , DeKosky Steve , Lopez Oscar L. , Feingold Eleanor , Kamboh M. Ilyas 
Published: December 2021

AbstractBackgroundCognitive decline is a major characteristic of aging and neurogenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease and other dementias. With worldwide increases in life‐expectancy and elderly population, cognitive decline is a major public health concern. Understanding genetic contributors to age‐related decline in cognition may facilitate identification of the molecular mechanisms of cognitive decline.MethodTo discover genetic influences on cognitive decline, we conducted genome‐wide meta‐analyses on longitudinal performance of five cognitive domains (attention, language, executive function, visuospatial, memory) and the global domain, constructed from five domains, using 3068 individuals aged 65 and above across three longitudinal cohorts: the Gingko biloba Memory Evaluation Study (GEMS), Monongahela‐Youghiogheny Healthy Aging Team (MYHAT) and Monongahela Valley Independent Elders Survey (MoVIES). A linear mixed effect model was used to find individual specific slopes by adjusting for baseline age, years of education and sex.Results
APOE*4 (rs429358), a well‐known risk factor for AD, demonstrated a genome‐wide significant association with the memory (P= 1.37E‐09) and global (P= 9.26E‐10) domains. Previous studies have also reported APOE*4 ‘s association with memory decline. In addition to APOE*4, multiple suggestive associations of gene loci with cognition were also observed for each domain as follows: attention on chromosome 9 near RASEF/FRMD3 (P = 8.29E‐08), memory on chromosome 6 near ID4/MBOAT1(P = 1.27E‐07), visuospatial function on chromosome 11 near PAMR (P = 2.74E‐07), language on chromosome 9 near PSAT1 (P = 4.08E‐07), executive function on chromosome 4 near SNHG27 (P = 6.49E‐07), and global function on chromosome 4 near LINC00290 (P=8.80E‐07).ConclusionOur result suggests that in addition to APOE, multiple genetic loci affect cognitive decline in older individuals. These findings may offer new insights into understanding the genetic architecture of cognitive decline.
INPP5D regulates the amyloid pathology in Alzheimer’s disease.
Authors: Lin Peter Bor‐Chian , Tsai Andy Po‐Yi , Nho Kwangsik , Lamb Bruce T. , Oblak Adrian L 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, robust microgliosis, neuroinflammation, and neuronal loss. Genome‐wide association studies highlighted a prominent role for microglia in late‐onset AD (LOAD). Specifically, inositol polyphosphate‐5‐phosphatase (INPP5D) is selectively expressed in brain microglia and one of its common intronic variants (rs35349669; OR=1.08, 95%CI=1.06‐1.11) has been reported to be associated with increased risk of LOAD. INPP5D is linked to the triggering receptor expressed on myeloid cells 2 (TREM2) signaling, but little is known about the function of INPP5D in microglia and how INPP5D regulates TREM2‐related AD pathogenesis. Therefore, we aim to understand the role of INPP5D in microglia and AD pathology.MethodWe performed differential gene expression analysis to investigate INPP5D expression in LOAD and its association with plaque density using transcriptomic (RNA‐Seq) data from the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP‐AD) cohort. We also performed quantitative real‐time PCR, immunoblotting, and immunofluorescence assays to assess INPP5D expression and microglial markers in the 5xFAD amyloid mouse model with INPP5D deficiency. Using the INPP5D knockout animal crossed with the 5xFAD, we perform the behavioral assays and IHC staining to reveal how the INPP5D regulates the amyloid pathology.Result
INPP5D gene expression was upregulated in LOAD and positively correlated with the amyloid plaque density. Inpp5d expression increased along with the disease progression in the 5xFAD mice, and is selectively expressed in plaque‐associated microglia. Also, Inpp5d inhibition mitigated the plaque burdens in the 5xFAD mice and further protected against behavioral deficits induced by amyloid pathology.ConclusionOur findings show that INPP5D expression increases throughout the AD progression and is predominantly in the plaque‐associated microglia. Importantly, inhibited INPP5D expression reduces amyloid pathology, highlighting INPP5D as a potential therapeutic target.
TasTest: Moving towards a digital screening test for pre‐clinical Alzheimer’s disease
Authors: Alty Jane , Bai Quan , George Rebecca J St , Bindoff Aiden , Li Renjie , Lawler Katherine , Hill Edward , Garg Saurabh , Bartlett Larissa , King Anna E , Vickers James C 
Published: December 2021

AbstractBackgroundThere is urgent need to develop population‐level digital biomarkers that can detect Alzheimer’s disease (AD) across the continuum, including the preclinical phase. This would allow risk stratification for specialist tests and early recruitment to clinical trials. Motor function declines in the preclinical phase but there has been little exploration of digital motor biomarkers. We have developed ‘TasTest’, an online test that assesses multiple cognitive domains, including movement. The aim of this study was to compare performance on TasTest with subtests of the Cambridge Neuropsychological Test Battery (CANTAB), a validated digital measure of cognitive decline, and determine how performance on the TasTest items varies with age in a large community sample of older adults.MethodThe TasTest items include measures of motor control (speed and coordination of keyboard tapping), processing speed (single and choice reaction time), attention and visual perception (identification of an animal in a distorted image), and visuospatial memory (identifying features from delayed recall of a complex figure). A total of 510 adults aged over 50 years (30% male; mean 65.5 years; SD 7.36), performed TasTest and CANTAB online assessments in their homes. We compared performance on TasTest items to performance on the Paired Associates Learning (PAL) task, which has been previously validated as predictive of accelerated cognitive decline (Barnett et al. 2015, Current Topics in Behavioral Neurosciences, vol 28, Springer, Cham).ResultAll TasTest items were significantly associated with PAL scores except the total number of correct responses on the reaction time tasks (Table 1). Several TasTest items had stronger correlations with age than the PAL, these included the keyboard tapping tasks, the number of correctly identified animals on the distorted image, and both simple and choice reaction times (Figure 1).ConclusionOlder people were able to readily complete TasTest tasks remotely from their homes, and performance on most items was significantly associated with scores on a previously validated test of cognition, and correlated with age. TasTest shows potential as a non‐invasive, scalable dementia screening tool.
Electrophysiological Examination of Executive Functioning in Lean and Obese Younger Adults
Authors: Larsen Brittany A , Klinedinst Brandon S , Grundy John , Willette Auriel A 
Published: December 2021

AbstractBackgroundObesity rates of adults in the United States have increased from 30.5% in 1999‐2000 to 42.4% in 2017‐2018, with a further projected prevalence to nearly 50% by 2030. Greater adiposity has been consistently associated with exacerbated brain atrophy and central glucose hypometabolism in prefrontal cortices that govern executive functions, including inhibitory control, working memory, emotion regulation, and cognitive flexibility. However, there is a paucity of research elucidating how neural physiology that governs these executive functions is impacted by obesity. Thus, our primary aim of this study was to investigate whether such electrophysiological changes due to obesity could be detected in healthy young adults.MethodIn this cross‐sectional study, we recruited 60 participants (18‐40 years, 55% female) and examined real‐time neural electrophysiology using electroencephalography (EEG) on 34 lean participants (mean body mass index (BMI)=22.1±2) and 26 overweight/obese participants (mean BMI=34.9±6.1) while they completed four cognitive tasks which separately focused on inhibitory control, working memory, emotion regulation, and cognitive flexibility. Serum proteomics were collected, and glycemic control was quantified from glycated hemoglobin (HbA1c) serum measures. We directly assessed body composition via dual energy X‐ray absorptiometry (DXA). Structural equation modeling was utilized in to probe direct/indirect associations between body composition, cardiometabolic biomarkers, and EEG waveforms.ResultAfter controlling for age, sex, HbA1c, and DXA android/gynoid ratio, we found that higher body fat percentage was associated with a significantly slower response in order to reach trough amplitudes on the FC1 electrode (196.3±134.4 milliseconds (ms) versus 204.4±311.1ms; β=0.94, p<0.001), as well as a significantly slower response in order to reach peak amplitudes on the FT7 electrode (215.9±129.9ms versus 334.1±327.2ms; β=‐0.537, p=0.019) during a Stroop task. Furthermore, we found that higher body fat associated with significantly slower responses in order to reach trough and peak amplitudes on the FT7 electrode (202.9±95.4ms versus 567.2±434.5ms, β=‐0.87, p=0.032; and 543.4±205.2ms versus 613±333.9ms, β=‐0.79, p=0.049, respectively) during an Operation Span task. No differences were observed between obese and lean subjects for emotion regulation or cognitive flexibility tasks.ConclusionYoung adults with greater adiposity may have impaired cognitive inhibition and decreased working memory capacity compared to lean counterparts.
The Best Approximation of an Objective State With a Given Set of Quantum States
Authors: Zhang Li‐qiang , Zhou Nan‐nan , Yu Chang‐shui 
Published: December 2021

AbstractApproximating a quantum state by the convex mixing of some given states has strong experimental significance and provides alternative understandings of quantum resource theory. It is essentially a complex optimal problem which, up to now, has only partially solved for qubit states. Here, the most general case is focused on that the approximation of a d‐dimensional objective quantum state by the given state set consisting of any number of (mixed‐) states. The problem is thoroughly solved with a closed solution of the minimal distance in the sense of l2 norm between the objective state and the set. In particular, the minimal number of states in the given set is presented to achieve the optimal distance. The validity of this closed solution is further verified numerically by several randomly generated quantum states.
Effect of drying method and wall material composition on the characteristics of camellia seed oil microcapsule powder
Authors: Song Fei , Li Yannan , Wang Bo , Shen Xiaojun , Wang Hui , Li Rui , Xia Qiuyu 
Published: December 2021

AbstractCamellia seed oil (CSO) is one of the richest sources of oleic acid (75–80%) and it is considered to provide beneficial health effects to humans. However, its susceptibility to oxidative degradation prevents its widespread use in the food industry. This study was aimed to improve the stability of camellia seed oil by microencapsulation. CSO was microencapsulated using whey protein concentrate (WPC) and maltodextrin (MD) or starch sodium octenylsuccinate (SSOS) as wall materials. The produced oil‐in‐water emulsion was subsequently dehydrated to produce microcapsule powder using spray and freeze drying techniques, respectively. Various characteristics of oil‐in‐water emulsion and final microcapsule powder including particle size distribution, encapsulation efficiency, morphology, rheological properties of reconstituted emulsions, in vitro digestion behavior and oxidative stability were determined to investigate the effect of wall material composition and drying method on these microcapsule powder characteristics. The spray‐dried powder had significantly higher bulk density and smoother surface compared to freeze‐dried powder while the freeze‐dried CSO microcapsule powder with WPC/SSOS as wall material had the highest encapsulation efficiency and the lowest surface oil. The subsequent in vitro digestion test suggested the microencapsulated CSO could be successfully controlled‐released in the simulated gastric (10.28–13.03%) and the subsequent intestinal fluid (72.89–89.61%). Oxidative stability of camellia seed oil was significantly improved by microencapsulation. The freeze dried CSO microcapsule powder in WPC/SSOS wall material exhibited highest encapsulation efficiency (95.17%) and best oxidative stability (peroxide value and p‐anisidine values of 3.57 meq/kg oil and 3.01, respectively, during the 45 days storage at 25°C.
Isocyanate‐free synthesis of ureas and polyureas via ruthenium catalyzed dehydrogenation of amines and formamides
Authors: Langsted Christopher R. , Paulson Samuel W. , Bomann Blake H. , Suhail Shanzay , Aguirre John A. , Saumer Emily J. , Baclasky Amelia R. , Salmon Kyle H. , Law Ariah C. , Farmer Ryan J. , Furchtenicht Casey J. , Stankowski Dakota S. , Johnson Mary L. , Corcoran Louis G. , Dolan Connor C. , Carney Michael J. , Robertson Nicholas J. 
Published: December 2021

AbstractEthyl formate is very effective for the formylation of amines and diamines to yield formamides and diformamides, respectively. Subsequent dehydrogenation of 1:1 mixtures of formamides and amines or diformamides and diamines with ruthenium pincer catalysts furnishes ureas and polyureas, respectively. This approach provides access to a large structural variety of ureas and polyureas because a wide range of primary amines and diamines are readily converted to the corresponding ureas and polyureas. Small molecule ureas were isolated in yields of up to 95%, whereas polyureas were isolated in lower yields (up to 68%) due to strong adhesion to the reaction flask and poor solubility impeding product removal. Furthermore, the ease with which hydrogen can be removed from the reaction medium enables the synthesis of polyureas with molecular weights that are among the highest reported to date (Mn up to 31,100 g mol−1). Notably, this synthetic approach does not necessitate high pressure conditions, simplifying equipment needed for their preparation, and it avoids the use of isocyanates, which have significant health concerns.
Palladium Nanoparticles Supported on Cellulosic Paper as Multifunctional Catalyst for Coupling and Hydrogenation Reactions
Authors: Kalanthoden Abdul Nasar , Zahir Md. Hasan , Aziz Md. Abdul , Al‐Najar Basmah , Rani S. Kutti , Shaikh M. Nasiruzzaman 
Published: December 2021

AbstractHallmark of a successful catalyst is its high efficiency, economic aspects, operational simplicity, extensive reusability, higher environment friendliness, and potential use in multiple industrial applications. Herein, a facile protocol involving a catalyst with Pd nanoparticles supported on cellulose paper (also known as a “dip‐catalyst”) for the hydrogenation of a series of quinolines, nitroarene, and C−C bond formation reactions in most benign solvents such as water is described. The mere insertion/removal of the “dip‐catalyst” strip enables instantaneous start/stop of the reaction, which enhances its reusability and ease of separation of products. Cellulose paper (CP) strips decorated with Pd nanoparticles (Pd/CP) are prepared by the reduction of K2PdCl4 soaked strips using formic acid as reductant. The resulting spherical shaped Pd particles, confirmed by scanning electron microscopy, form stable catalysis centers on the support. XRD signature confirms the crystallinity of the Pd nanoparticles and the TEM images display 15–20 nm size particles uniformly decorating CP. X‐ray photoelectron spectroscopy indicates the formation of metallic Pd. The catalyst is tested for the C−C bond formation reactions. Pd/CP catalyzed Suzuki‐Miyaura coupling reaction demonstrate >99% conversion with optimum selectivity. On the other hand, Mizoroki‐Heck reaction produced 87% conversion with the reaction of 4‐methoxycarbonyl phenylboronic acid and iodobenzene in ethanol:water (1 : 1 v/v) using KOH as base. The developed Pd/CP construct produces >99% of the pyridine‐ring hydrogenated product on quinoline hydrogenation using tetrahydroxydiboron (THDB) as the hydrogen source. Diverse and highly reducible functional groups were also evaluated for transfer hydrogenation, which demonstrates a high efficiency in terms of both reactivity and selectivity. The used catalysts are recyclable for the multiple cycles.
Adaptive finite‐time cooperative platoon control of connected vehicles under actuator saturation
Authors: Gao Zhenyu , Zhang Yi , Liu Qingmeng 
Published: December 2021

AbstractThis paper investigates cooperative platoon control of connected vehicles subject to parameter uncertainties, external disturbances, and actuator saturation. Firstly, a approximation method based on radial basis function neural network (RBFNN) is employed to approximate the nonlinear vehicle dynamics and adaptive estimation laws are introduced to tackle the environment disturbances and the unknown upper bound of the actuator saturation, external disturbances and actuator saturation.Then, based on the backstepping technique, compensator‐based command filter and the finite time theory, a robust finite‐time cooperative controller is proposed, with which the tracking error will converge to a small region of origin within settling time. Namely, the given control method can guarantee all the signals in the control system to be finite‐time stabilized. Besides, the problem of “explosion of complexity” in backstepping control is solved by command filter technique. Finally, the correctness and effectiveness of the proposed control scheme is demonstrated by numerical simulations.