bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis of prokaryotic ubiquitin-like protein engagement and translocation by the mycobacterial Mpa-proteasome complex
Authors: Kavalchuk Mikhail , Jomaa Ahmad , Müller Andreas U. , Weber-Ban Eilika 
Published: January 2022

AbstractProteasomes are present in eukaryotes, archaea and Actinobacteria, including the human pathogenMycobacterium tuberculosis, where proteasomal degradation supports persistence inside the host. In mycobacteria and other members of Actinobacteria, prokaryotic ubiquitin-like protein (Pup) serves as a degradation tag post-translationally conjugated to target proteins for their recruitment to the mycobacterial proteasome ATPase (Mpa). Here, we use single-particle cryo-electron microscopy to determine the structure of Mpa in complex with the 20S core particle at an early stage of pupylated substrate recruitment, shedding light on the mechanism of substrate translocation. Two conformational states of Mpa show how substrate is translocated stepwise towards the degradation chamber of the proteasome core particle. We also demonstrate, in vitro and in vivo, the importance of a structural feature in Mpa that allows formation of alternating charge-complementary interactions with the proteasome resulting in radial, rail-guided movements during the ATPase conformational cycle.
Multifactorial engineering of biomimetic membranes for batteries with multiple high-performance parameters
Authors: Wang Mingqiang , Emre Ahmet E. , Kim Ji-Young , Huang Yiting , Liu Li , Cecen Volkan , Huang Yudong , Kotov Nicholas A. 
Published: January 2022

AbstractLithium–sulfur (Li–S) batteries have a high specific capacity, but lithium polysulfide (LPS) diffusion and lithium dendrite growth drastically reduce their cycle life. High discharge rates also necessitate their resilience to high temperature. Here we show that biomimetic self-assembled membranes from aramid nanofibers (ANFs) address these challenges. Replicating the fibrous structure of cartilage, multifactorial engineering of ion-selective mechanical, and thermal properties becomes possible. LPS adsorption on ANF surface creates a layer of negative charge on nanoscale pores blocking LPS transport. The batteries using cartilage-like bioinspired ANF membranes exhibited a close-to-theoretical-maximum capacity of 1268 mAh g−1, up to 3500+ cycle life, and up to 3C discharge rates. Essential for safety, the high thermal resilience of ANFs enables operation at temperatures up to 80 °C. The simplicity of synthesis and recyclability of ANFs open the door for engineering high-performance materials for numerous energy technologies.
Manipulation and control of droplets on surfaces in a homogeneous electric field
Authors: Hartmann Johannes , Schür Maximilian T. , Hardt Steffen 
Published: January 2022

AbstractA method to manipulate and control droplets on a surface is presented. The method is based on inducing electric dipoles inside the droplets using a homogeneous external electric field. It is shown that the repulsive dipole force efficiently suppresses the coalescence of droplets moving on a liquid-infused surface (LIS). Using a combination of experiments, numerical computations and semi-analytical models, the dependence of the repulsion force on the droplet volumes, the distance between the droplets and the electric field strength is revealed. The method allows to suppress coalescence in complex multi-droplet flows and is real-time adaptive. When the electric field strength exceeds a critical value, tip streaming from the droplets sets in. Based on that, it becomes possible to withdraw minute samples from an array of droplets in a parallel process.
NuA4 and H2A.Z control environmental responses and autotrophic growth in Arabidopsis
Authors: Bieluszewski Tomasz , Sura Weronika , Dziegielewski Wojciech , Bieluszewska Anna , Lachance Catherine , Kabza Michał , Szymanska-Lejman Maja , Abram Mateusz , Wlodzimierz Piotr , De Winne Nancy , De Jaeger Geert , Sadowski Jan , Côté Jacques , Ziolkowski Piotr A. 
Published: January 2022

AbstractNucleosomal acetyltransferase of H4 (NuA4) is an essential transcriptional coactivator in eukaryotes, but remains poorly characterized in plants. Here, we describe Arabidopsis homologs of the NuA4 scaffold proteins Enhancer of Polycomb-Like 1 (AtEPL1) and Esa1-Associated Factor 1 (AtEAF1). Loss of AtEAF1 results in inhibition of growth and chloroplast development. These effects are stronger in the Atepl1 mutant and are further enhanced by loss of Golden2-Like (GLK) transcription factors, suggesting that NuA4 activates nuclear plastid genes alongside GLK. We demonstrate that AtEPL1 is necessary for nucleosomal acetylation of histones H4 and H2A.Z by NuA4 in vitro. These chromatin marks are diminished genome-wide in Atepl1, while another active chromatin mark, H3K9 acetylation (H3K9ac), is locally enhanced. Expression of many chloroplast-related genes depends on NuA4, as they are downregulated with loss of H4ac and H2A.Zac. Finally, we demonstrate that NuA4 promotes H2A.Z deposition and by doing so prevents spurious activation of stress response genes.
Dynamic targeting enables domain-general inhibitory control over action and thought by the prefrontal cortex
Authors: Apšvalka Dace , Ferreira Catarina S. , Schmitz Taylor W. , Rowe James B. , Anderson Michael C. 
Published: January 2022

AbstractOver the last two decades, inhibitory control has featured prominently in accounts of how humans and other organisms regulate their behaviour and thought. Previous work on how the brain stops actions and thoughts, however, has emphasised distinct prefrontal regions supporting these functions, suggesting domain-specific mechanisms. Here we show that stopping actions and thoughts recruits common regions in the right dorsolateral and ventrolateral prefrontal cortex to suppress diverse content, via dynamic targeting. Within each region, classifiers trained to distinguish action-stopping from action-execution also identify when people are suppressing their thoughts (and vice versa). Effective connectivity analysis reveals that both prefrontal regions contribute to action and thought stopping by targeting the motor cortex or the hippocampus, depending on the goal, to suppress their task-specific activity. These findings support the existence of a domain-general system that underlies inhibitory control and establish Dynamic Targeting as a mechanism enabling this ability.
Chromosomal microarray analysis of 410 Han Chinese patients with autism spectrum disorder or unexplained intellectual disability and developmental delay
Authors: Liu Yi , Lv Yuqiang , Zarrei Mehdi , Dong Rui , Yang Xiaomeng , Higginbotham Edward J. , Li Yue , Zhao Dongmei , Song Fengling , Yang Yali , Zhang Haiyan , Wang Ying , Scherer Stephen W. , Gai Zhongtao 
Published: January 2022

AbstractCopy number variants (CNVs) are recognized as a crucial genetic cause of neurodevelopmental disorders (NDDs). Chromosomal microarray analysis (CMA), the first-tier diagnostic test for individuals with NDDs, has been utilized to detect CNVs in clinical practice, but most reports are still from populations of European ancestry. To contribute more worldwide clinical genomics data, we investigated the genetic etiology of 410 Han Chinese patients with NDDs (151 with autism and 259 with unexplained intellectual disability (ID) and developmental delay (DD)) using CMA (Affymetrix) after G-banding karyotyping. Among all the NDD patients, 109 (26.6%) carried clinically relevant CNVs or uniparental disomies (UPDs), and 8 (2.0%) had aneuploidies (6 with trisomy 21 syndrome, 1 with 47,XXY, 1 with 47,XYY). In total, we found 129 clinically relevant CNVs and UPDs, including 32 CNVs in 30 ASD patients, and 92 CNVs and 5 UPDs in 79 ID/DD cases. When excluding the eight patients with aneuploidies, the diagnostic yield of pathogenic and likely pathogenic CNVs and UPDs was 20.9% for all NDDs (84/402), 3.3% in ASD (5/151), and 31.5% in ID/DD (79/251). When aneuploidies were included, the diagnostic yield increased to 22.4% for all NDDs (92/410), and 33.6% for ID/DD (87/259). We identified a de novo CNV in 14.9% (60/402) of subjects with NDDs. Interestingly, a higher diagnostic yield was observed in females (31.3%, 40/128) compared to males (16.1%, 44/274) for all NDDs (P = 4.8 × 10−4), suggesting that a female protective mechanism exists for deleterious CNVs and UPDs.
Toroidal topology of population activity in grid cells
Authors: Gardner Richard J. , Hermansen Erik , Pachitariu Marius , Burak Yoram , Baas Nils A. , Dunn Benjamin A. , Moser May-Britt , Moser Edvard I. 
Published: January 2022

AbstractThe medial entorhinal cortex is part of a neural system for mapping the position of an individual within a physical environment1. Grid cells, a key component of this system, fire in a characteristic hexagonal pattern of locations2, and are organized in modules3 that collectively form a population code for the animal’s allocentric position1. The invariance of the correlation structure of this population code across environments4,5 and behavioural states6,7, independent of specific sensory inputs, has pointed to intrinsic, recurrently connected continuous attractor networks (CANs) as a possible substrate of the grid pattern1,8–11. However, whether grid cell networks show continuous attractor dynamics, and how they interface with inputs from the environment, has remained unclear owing to the small samples of cells obtained so far. Here, using simultaneous recordings from many hundreds of grid cells and subsequent topological data analysis, we show that the joint activity of grid cells from an individual module resides on a toroidal manifold, as expected in a two-dimensional CAN. Positions on the torus correspond to positions of the moving animal in the environment. Individual cells are preferentially active at singular positions on the torus. Their positions are maintained between environments and from wakefulness to sleep, as predicted by CAN models for grid cells but not by alternative feedforward models12. This demonstration of network dynamics on a toroidal manifold provides a population-level visualization of CAN dynamics in grid cells.
Mutation bias reflects natural selection in Arabidopsis thaliana
Authors: Monroe J. Grey , Srikant Thanvi , Carbonell-Bejerano Pablo , Becker Claude , Lensink Mariele , Exposito-Alonso Moises , Klein Marie , Hildebrandt Julia , Neumann Manuela , Kliebenstein Daniel , Weng Mao-Lun , Imbert Eric , Ågren Jon , Rutter Matthew T. , Fenster Charles B. , Weigel Detlef 
Published: January 2022

AbstractSince the first half of the twentieth century, evolutionary theory has been dominated by the idea that mutations occur randomly with respect to their consequences1. Here we test this assumption with large surveys of de novo mutations in the plant Arabidopsis thaliana. In contrast to expectations, we find that mutations occur less often in functionally constrained regions of the genome—mutation frequency is reduced by half inside gene bodies and by two-thirds in essential genes. With independent genomic mutation datasets, including from the largest Arabidopsis mutation accumulation experiment conducted to date, we demonstrate that epigenomic and physical features explain over 90% of variance in the genome-wide pattern of mutation bias surrounding genes. Observed mutation frequencies around genes in turn accurately predict patterns of genetic polymorphisms in natural Arabidopsis accessions (r = 0.96). That mutation bias is the primary force behind patterns of sequence evolution around genes in natural accessions is supported by analyses of allele frequencies. Finally, we find that genes subject to stronger purifying selection have a lower mutation rate. We conclude that epigenome-associated mutation bias2 reduces the occurrence of deleterious mutations in Arabidopsis, challenging the prevailing paradigm that mutation is a directionless force in evolution.
Age of the oldest known Homo sapiens from eastern Africa
Authors: Vidal Céline M. , Lane Christine S. , Asrat Asfawossen , Barfod Dan N. , Mark Darren F. , Tomlinson Emma L. , Tadesse Amdemichael Zafu , Yirgu Gezahegn , Deino Alan , Hutchison William , Mounier Aurélien , Oppenheimer Clive 
Published: January 2022

AbstractEfforts to date the oldest modern human fossils in eastern Africa, from Omo-Kibish1–3 and Herto4,5 in Ethiopia, have drawn on a variety of chronometric evidence, including 40Ar/39Ar ages of stratigraphically associated tuffs. The ages that are generally reported for these fossils are around 197 thousand years (kyr) for the Kibish Omo I3,6,7, and around 160–155 kyr for the Herto hominins5,8. However, the stratigraphic relationships and tephra correlations that underpin these estimates have been challenged6,8. Here we report geochemical analyses that link the Kamoya’s Hominid Site (KHS) Tuff9, which conclusively overlies the member of the Omo-Kibish Formation that contains Omo I, with a major explosive eruption of Shala volcano in the Main Ethiopian Rift. By dating the proximal deposits of this eruption, we obtain a new minimum age for the Omo fossils of 233 ± 22 kyr. Contrary to previous arguments6,8, we also show that the KHS Tuff does not correlate with another widespread tephra layer, the Waidedo Vitric Tuff, and therefore cannot anchor a minimum age for the Herto fossils. Shifting the age of the oldest known Homo sapiens fossils in eastern Africa to before around 200 thousand years ago is consistent with independent evidence for greater antiquity of the modern human lineage10.
Cefotax-magnetic nanoparticles as an alternative approach to control Methicillin-Resistant Staphylococcus aureus (MRSA) from different sources
Authors: Mohamed Manar Bahaa El Din , Abo El-Ela Fatma I. , Mahmoud Rehab K. , Farghali Ahmed A. , Gamil Shymaa , Aziz Sahar Abdel Aleem Abdel 
Published: January 2022

AbstractThis study aimed to evaluate the efficacy of magnetic nanocomposite of cefotax against MRSA. A total of 190 samples were collected from milk, farm personnel and different environmental components from the dairy farm under the study to isolate S. aureus. Cefotax based magnetic nanoparticles was synthetized by the adsorption method and marked using Fourier-transform infrared spectrum (FT-IR), and X-ray diffraction (XRD), then it was characterized using Scanning and Transmission Electron Microscope (SEM and TEM). The obtained results revealed that number of positive samples of S. aureus isolation were 63 (33.1%), mainly from feed manger followed by milk machine swabs (60.0 and 53.3%, respectively) at X2 = 48.83 and P < 0.001. Obtained isolates were identified biochemically and by using molecular assays (PCR), also mec A gene responsible for resistance to cefotax was detected. Testing the sensitivity of 63 isolates of S. aureus showed variable degree of resistance to different tested antibiotics and significant sensitivity to cefotax based magnetic nanoparticles at P < 0.05. It was concluded that dairy environment might act a potential source for transmission of MRSA between human and animal populations. In addition, cefotax based magnetic nanoparticles verified an extreme antimicrobial efficacy against MRSA.
Mechanical work accounts for most of the energetic cost in human running
Authors: Riddick R. C. , Kuo A. D. 
Published: January 2022

AbstractThe metabolic cost of human running is not well explained, in part because the amount of work performed actively by muscles is largely unknown. Series elastic tissues such as tendon can save energy by performing work passively, but there are few direct measurements of the active versus passive contributions to work in running. There are, however, indirect biomechanical measures that can help estimate the relative contributions to overall metabolic cost. We developed a simple cost estimate for muscle work in humans running (N = 8) at moderate speeds (2.2–4.6 m/s) based on measured joint mechanics and passive dissipation from soft tissue deformations. We found that even if 50% of the work observed at the lower extremity joints is performed passively, active muscle work still accounts for 76% of the net energetic cost. Up to 24% of this cost compensates for the energy lost in soft tissue deformations. The estimated cost of active work may be adjusted based on assumptions of multi-articular energy transfer, elasticity, and muscle efficiency, but even conservative assumptions yield active work costs of at least 60%. Passive elasticity can reduce the active work of running, but muscle work still explains most of the overall energetic cost.
Usefulness of circulating tumor DNA by targeting human papilloma virus-derived sequences as a biomarker in p16-positive oropharyngeal cancer
Authors: Akashi Ken , Sakai Toshihiko , Fukuoka Osamu , Saito Yuki , Yoshida Masafumi , Ando Mizuo , Ito Takeshi , Murakami Yoshinori , Yamasoba Tatsuya 
Published: January 2022

AbstractIn head and neck cancer, early detection of recurrence after treatment is important. The contemporary development of therapeutic agents have improved the prognosis after recurrence; however, no biomarker has been established for evaluating therapeutic effects or detecting recurrence. Recently, circulating tumor DNA (ctDNA), which comprises DNA derived from tumor cells and exists in the form of cell-free DNA in the blood, has attracted attention as a minimally invasive and repeatable biomarker for detecting cancer. We validated the usefulness of ctDNA of human papilloma virus (HPV)-derived sequences as a biomarker in HPV-related p16-positive oropharyngeal cancer by assessing 25 patients with p16-positive oropharyngeal cancer. Blood samples were collected from each patient at multiple time points during the treatment, and the plasma was preserved. The ctDNA was extracted from the plasma and analyzed using digital polymerase chain reaction. HPV-derived ctDNA was detected in 14 (56%) of the 25 patients. In all the patients, the samples were found to be ctDNA-negative after initial treatment. Cancer recurrence was observed in 2 of the 14 patients; HPV-derived ctDNA was detected at the time of recurrence. Our results indicate that HPV-derived ctDNA can be a prospective biomarker for predicting the recurrence of p16-positive oropharyngeal cancer.
Thermally controlled microfluidic back pressure regulator
Authors: Svensson Karolina , Södergren Simon , Hjort Klas 
Published: January 2022

AbstractBy using the temperature dependence of viscosity, we introduce a novel type of microfluidic lab-on-a-chip back pressure regulator (BPR) that can be integrated into a micro-total-analysis-system. A BPR is an important component used to gain pressure control and maintain elevated pressures in e.g. chemical extractions, synthesis, and analyses. Such applications have been limited in microfluidics, since the back pressure regularly has been attained by passive restrictors or external large-scale BPRs. Herein, an active microfluidic BPR is presented, consisting of a glass chip with integrated thin-film heaters and thermal sensors. It has no moving parts but a fluid restrictor where the flow resistance is controlled by the change of viscosity with temperature. Performance was evaluated by regulating the upstream pressure of methanol or water using a PID controller. The developed BPR has the smallest reported dead volume of 3 nL and the thermal actuation has time constants of a few seconds. The pressure regulation were reproducible with a precision in the millibar range, limited by the pressure sensor. The time constant of the pressure changes was evaluated and its dependence of the total upstream volume and the compressibility of the liquids is introduced.
Association of red blood cell and platelet transfusions with persistent inflammation, immunosuppression, and catabolism syndrome in critically ill patients
Authors: Suzuki Ginga , Ichibayashi Ryo , Masuyama Yuka , Yamamoto Saki , Serizawa Hibiki , Nakamichi Yoshimi , Watanabe Masayuki , Honda Mitsuru 
Published: January 2022

AbstractThe objective of this single-center retrospective cohort study was to investigate the relationship between blood transfusion and persistent inflammation, immunosuppression, and catabolism syndrome (PIICS). The study was conducted at the Critical Care Center at Toho University Omori Medical Center, Japan. We included 391 patients in the PIICS group (hospitalization for > 15 days, C-reactive protein > 3.0 mg/dL or albumin < 3.0 mg/dL or lymph < 800/μL on day 14) and 762 patients in the non-PIICS group (hospitalization for > 15 days and not meeting the PIICS criteria). We performed univariate and multivariate logistic regression analyses using PIICS as the objective variable and red blood cell (RBC) or fresh frozen plasma or platelet (PLT) transfusion and other confounding factors as explanatory variables. In addition, we conducted a sensitivity analysis using propensity score matching analysis. The multivariate and propensity score analyses showed that RBC and PLT transfusions were significantly associated with PIICS. This is the first study to report an association between RBC and PLT transfusions and PIICS. Our findings have contributed to better understanding the risk factors of PIICS and suggest that physicians should consider the risk of PIICS occurrence when administering blood transfusions in intensive care unit (ICU) patients.
A multi-omics study of circulating phospholipid markers of blood pressure
Authors: Liu Jun , de Vries Paul S. , Del Greco M. Fabiola , Johansson Åsa , Schraut Katharina E. , Hayward Caroline , van Dijk Ko Willems , Franco Oscar. H. , Hicks Andrew A. , Vitart Veronique , Rudan Igor , Campbell Harry , Polašek Ozren , Pramstaller Peter P. , Wilson James F. , Gyllensten Ulf , van Duijn Cornelia M. , Dehghan Abbas , Demirkan Ayşe 
Published: January 2022

AbstractHigh-throughput techniques allow us to measure a wide-range of phospholipids which can provide insight into the mechanisms of hypertension. We aimed to conduct an in-depth multi-omics study of various phospholipids with systolic blood pressure (SBP) and diastolic blood pressure (DBP). The associations of blood pressure and 151 plasma phospholipids measured by electrospray ionization tandem mass spectrometry were performed by linear regression in five European cohorts (n = 2786 in discovery and n = 1185 in replication). We further explored the blood pressure-related phospholipids in Erasmus Rucphen Family (ERF) study by associating them with multiple cardiometabolic traits (linear regression) and predicting incident hypertension (Cox regression). Mendelian Randomization (MR) and phenome-wide association study (Phewas) were also explored to further investigate these association results. We identified six phosphatidylethanolamines (PE 38:3, PE 38:4, PE 38:6, PE 40:4, PE 40:5 and PE 40:6) and two phosphatidylcholines (PC 32:1 and PC 40:5) which together predicted incident hypertension with an area under the ROC curve (AUC) of 0.61. The identified eight phospholipids are strongly associated with triglycerides, obesity related traits (e.g. waist, waist-hip ratio, total fat percentage, body mass index, lipid-lowering medication, and leptin), diabetes related traits (e.g. glucose, insulin resistance and insulin) and prevalent type 2 diabetes. The genetic determinants of these phospholipids also associated with many lipoproteins, heart rate, pulse rate and blood cell counts. No significant association was identified by bi-directional MR approach. We identified eight blood pressure-related circulating phospholipids that have a predictive value for incident hypertension. Our cross-omics analyses show that phospholipid metabolites in the circulation may yield insight into blood pressure regulation and raise a number of testable hypothesis for future research.