bluuebunny/crossref_metadata_2025 huggingface dataset:
Reference signal extraction based on multiprocessing method in dual-polarization antenna passive radar
Authors: Yi Yucheng , Zhu Lu , Liang Long , Fu Yan
Published: November 2022

Extraction of reference signal is an indispensable step in the signal processing of polarization diversity passive radar (PDPR) based on a digital television signal. A conventional reference signal extraction method requires an additional reference antenna, which has a certain demand for space. Single dual-polarization antenna passive radar (SDPPR) systems do not require a reference antenna, and the radar station layout is flexible, which is suitable for a large-scale radar network. It is a main research direction of PDPR in future. However, its reference signal extraction needs to rely on the signal reconstruction method. When the signal to interference and noise ratio of the direct-path signal is relatively low, the signal reconstruction method will fail. In this paper, we propose a reference signal extraction method based on sub-carrier processing method, blind adaptive oblique projection technology, and extensive cancelation algorithm to solve the above problem. Experimental results show that the method proposed in this paper is a reasonable alternative after the failure of reference signal reconstruction, and it is an effective supplement to the reference signal extraction technology.
Betreuung durch eine Advanced Practice Nurse: Erfahrungen von Patient_innen mit Sarkom und Angehörigen
Authors: Bologna Filomena , Kaufmann Sabine , Staudacher Sandra , Spichiger Elisabeth
Published: November 2022

Zusammenfassung. Hintergrund: Sarkome sind eine heterogene Gruppe von seltenen, malignen Tumoren mit unterschiedlichen Verläufen, die das Leben von Patient_innen und Angehörigen erheblich belasten. Aufgrund der komplexen Behandlungen erfolgt die Betreuung der Betroffenen am Sarkomzentrum eines Schweizer Universitätsspitals durch ein interprofessionelles Team. Die Advanced Practice Nurse (APN) ist ein Mitglied des interprofessionellen Teams und betreut Patient_innen und Angehörige über den ganzen Krankheitsverlauf. Bisher wurde die Betreuung durch eine APN aus Sicht von Patient_innen mit Sarkom und Angehörigen in der Literatur wenig beschrieben. Ziel: Es wurde untersucht, wie Patient_innen mit Sarkom und Angehörige die Betreuung durch die APN erlebt hatten. Methoden: Die Studie orientierte sich an der qualitativen Forschungsmethodologie „Interpretive Description“. Einzelinterviews mit sieben Patient_innen und fünf Angehörigen wurden durchgeführt und in einem iterativen Prozess analysiert. Ergebnisse: Für Patient_innen und Angehörige war die Zeit von der Diagnose bis zur Therapie und Nachsorge sehr belastend. Sie erlebten die Betreuung durch die APN während dieser Zeit als große Unterstützung und beschrieben die APN als mitfühlende Vertrauens- und kontinuierliche Ansprechperson, die kompetent vernetzte, informierte und beriet. Schlussfolgerungen: Für Patient_innen mit Sarkomerkrankungen und Angehörige war eine kontinuierliche Ansprech- und mitfühlende, sehr fachkompetente Vertrauensperson wesentlich. Eine APN kann mit ihrer Betreuung diesem Anspruch gerecht werden.
Modeling Seismic Recordings of High‐Frequency Guided Infrasound on Mars
Authors: Xu Zongbo , Froment Marouchka , Garcia Raphaël F. , Beucler Éric , Onodera Keisuke , Kawamura Taichi , Lognonné Philippe , Banerdt William Bruce
Published: November 2022

NASA's Interior Exploration using Seismic Investigations, Geodesy and Heat Transport (InSight) mission records several high‐frequency (>0.5 Hz) dispersive seismic signals on Mars. These signals are due to the acoustic‐to‐seismic coupling of infrasound generated by the entry and impact of meteorites. This dispersion property is due to infrasound propagating in a structured atmosphere, and we refer to this dispersive infrasound as guided infrasound. We propose to model the propagation of guided infrasound and the seismic coupling to the ground analytically; we use a 1D layered atmosphere on a three‐layer solid subsurface medium. The synthetic ground movements fit the observed dispersive seismic signals well and the fitting indicates that the regolith beneath InSight is about 40‐m in thickness. We also examine and validate the previously‐published subsurface models derived from InSight ambient seismic vibration data.
Pramipexole modulates fronto-subthalamic pathway in sequential working memory
Authors: Heldmann Marcus , Mönch Eliana , Kesseböhmer Antonia , Brüggemann Norbert , Münte Thomas F. , Ye Zheng
Published: November 2022

Brain dopamine may regulate the ability to maintain and manipulate sequential information online. However, the precise role of dopamine remains unclear. This pharmacological fMRI study examined whether and how the dopamine D2/3 receptor agonist pramipexole modulates fronto-subthalamic or fronto-striatal pathways during sequential working memory. This study used a double-blind, randomized crossover design. Twenty-two healthy male volunteers completed a digit ordering task during fMRI scanning after receiving a single oral dose of 0.5-mg pramipexole or placebo. The pramipexole effects on task performance, regional activity, activity pattern similarity, and functional connectivity were analyzed. Pramipexole impaired task performance, leading to less accurate and slower responses in the digit ordering task. Also, it downregulated the maintenance-related subthalamic and dorsolateral prefrontal activity, increasing reaction times for maintaining sequences. In contrast, pramipexole upregulated the manipulation-related subthalamic and dorsolateral prefrontal activity, increasing reaction time costs for manipulating sequences. In addition, it altered the dorsolateral prefrontal activity pattern similarity and fronto-subthalamic functional connectivity. Finally, pramipexole reduced maintenance-related striatal activity, which did not affect the behavior. This study confirms the role of the fronto-subthalamic pathway in sequential working memory. Furthermore, it shows that D2 transmission can regulate sequential working memory by modulating the fronto-subthalamic pathway.
Feasibility of home hand rehabilitation using musicglove after chronic spinal cord injury
Authors: Sanders Quentin , Chan Vicky , Augsburger Renee , Cramer Steven C. , Reinkensmeyer David J. , Sharp Kelli
Published: November 2022

Study design

Randomized, controlled single-blind cross over study. This study was registered on ClinicalTrials.gov (NCT02473614).

Objectives

Examine usership patterns and feasibility of MusicGlove for at home hand rehabilitation therapy following chronic spinal cord injury.

Setting

Homes of participants.

Methods

Ten participants with chronic spinal cord injury completed two baseline assessments of hand function. After a stable baseline was determined all participants were randomized into two groups: Experimental and Control. Each group was given a recommended therapy dosage. Following this participants switched interventions.

Results

On average participants had higher levels of compliance (6.1 ± 3.5 h.), and completed more grips (15,760 ± 9,590 grips) compared to participants in previous stroke studies using the same device. Participants modulated game parameters in a manner consistent with optimal challenge principles from motor learning theory. Participants in the experimental group increased their prehension ability (1 ± 1.4 MusicGlove, 0.2 ± 0.5 Control) and performance (1.4 ± 2.2 MusicGlove, 0.4 ± 0.55 Control) on the Graded and Redefined Assessment of Strength, Sensibility, and Prehension subtests. Increases in performance on the Box and Blocks Test also favored the experimental group compared to the conventional group at the end of therapy (4.2 ± 5.9, −1.0 ± 3.4 respectively).

Conclusions

MusicGlove is a feasible option for hand therapy in the home-setting for individuals with chronic SCI. Participants completed nearly twice as many gripping movements compared to individuals from the sub-acute and chronic stroke populations, and a number far greater than the number of movements typically achieved during traditional rehabilitation.
Pro- and anti-inflammatory cytokines Interleukin-6 and Interleukin-10 predict therapy outcome of female patients with posttraumatic stress disorder
Authors: Renner Vanessa , Joraschky Peter , Kirschbaum Clemens , Schellong Julia , Petrowski Katja
Published: November 2022

PTSD patients show alterations of the immune system, mainly a ‘low-grade inflammation’. Psychotherapeutic treatments are meant to reduce symptom burden of PTSD patients but 30–50% of PTSD patients do not benefit from psychotherapy. Therefore, in this study, the predictive effect of cytokine levels on therapy outcome are investigated. Pro- (IL-6) and anti-inflammatory (IL-10) cytokines in female PTSD patients (N = 17) were assessed under acute stress during a Trier social stress test (TSST) before therapeutic treatment. The predictive effects of IL-6 and IL-10 on therapy outcome (SCL_GSI, BDI) after an inpatient psychotherapeutic treatment at the University Medical Center Carl Gustav Carus, Technische Universität Dresden was investigated. Areas under the curve with respect to ground (AUCG) and increase (AUCI) for IL-6 and IL-10 levels during the TSST were calculated and used as predictors in regression analyses with pre-treatment scores. Models including all three predictors show good model fits (R2 = 0.255 to 0.744). Models including AUCG and AUCI scores show superior fits compared with models including pre-treatment scores alone (ΔR2 = 0.196 to 0.444). IL-6 AUCG and AUCI scores are significant predictors for post-treatment SCL-GSI and BDI (β = −0.554 to 0.853), whereas IL-10 AUCG significantly predicts SCL-GSI and BDI (β = −0.449 to −0.509). Therefore, pro- and anti-inflammatory IL-6 and IL-10 levels under acute stress before therapy predict therapy outcome of female PTSD patients regarding general symptom burden and depressive symptoms. Future studies should further address the link between inflammation and therapy outcome, especially underlying mechanisms and influencing factors.
LncRNA HOXA11-AS promotes glioma malignant phenotypes and reduces its sensitivity to ROS via Tpl2-MEK1/2-ERK1/2 pathway
Authors: Wei Cheng , Zhang Xiaoyang , Peng Dazhao , Zhang Xu , Guo Haizhen , Lu Yalin , Luo Lin , Wang Bo , Li Zesheng , He Yingjie , Du Xuezhi , Zhang Shu , Liang Hao , Li Shenghui , Wang Sheng , Han Lei , Zhang Jianning
Published: November 2022

Our previous studies showed that dysregulation of the long noncoding RNA (lncRNA) HOXA11-AS plays an important role in the development of glioma. However, the molecular mechanism of HOXA11-AS in glioma remains largely unknown. In this study, we explore the molecular mechanisms underlying abnormal expression and biological function of HOXA11-AS for identifying novel therapeutic targets in glioma. The expression of HOXA11-AS, and the relationship between HOXA11-AS and the prognosis of glioma patients were analyzed using databases and glioma samples. Transcriptomics, proteomics, RIP, ChIRP, luciferase, and ChIP assays were used to explore its upstream and downstream targets in glioma. The role of HOXA11-AS in regulating the sensitivity of glioma cells to reactive oxygen species (ROS) was also investigated in vitro and in vivo. We found that HOXA11-AS was significantly upregulated in glioma, and was correlated with the poor prognosis of glioma patients. Ectopic expression of HOXA11-AS promoted the proliferation, migration, and invasion of glioma cells in vitro and in vivo. Mechanistically, HOXA11-AS acted as a molecular sponge for let-7b-5p in the cytoplasm, antagonizing its ability to repress the expression of CTHRC1, which activates the β-catenin/c-Myc pathway. In addition, c-Myc was involved in HOXA11-AS dysregulation via binding to its promoter region to form a self-activating loop. HOXA11-AS, functioned as a scaffold in the nucleus, also recruited transcription factor c-Jun to the Tpl2 promoter, which activates the Tpl2-MEK1/2-ERK1/2 pathway to promote ROS resistance in glioma. Importantly, HOXA11-AS knockdown could sensitize glioma cells to ROS. Above, oncogenic HOXA11-AS upregulates CTHRC1 expression as a ceRNA by adsorbing let-7b-5p, which activates c-Myc to regulate itself transcription. HOXA11-AS knockdown promotes ROS sensitivity in glioma cells by regulating the Tpl2-MEK1/2-ERK1/2 axis, demonstrating that HOXA11-AS may be translated to increase ROS sensitivity therapeutically.
Identification of TFPI as a receptor reveals recombination-driven receptor switching in Clostridioides difficile toxin B variants
Authors: Tian Songhai , Xiong Xiaozhe , Zeng Ji , Wang Siyu , Tremblay Benjamin Jean-Marie , Chen Peng , Chen Baohua , Liu Min , Chen Pengsheng , Sheng Kuanwei , Zeve Daniel , Qi Wanshu , Breault David T. , Rodríguez César , Gerhard Ralf , Jin Rongsheng , Doxey Andrew C. , Dong Min
Published: November 2022

Toxin B (TcdB) is a major exotoxin responsible for diseases associated with Clostridioides difficile infection. Its sequence variations among clinical isolates may contribute to the difficulty in developing effective therapeutics. Here, we investigate receptor-binding specificity of major TcdB subtypes (TcdB1 to TcdB12). We find that representative members of subtypes 2, 4, 7, 10, 11, and 12 do not recognize the established host receptor, frizzled proteins (FZDs). Using a genome-wide CRISPR-Cas9-mediated screen, we identify tissue factor pathway inhibitor (TFPI) as a host receptor for TcdB4. TFPI is recognized by a region in TcdB4 that is homologous to the FZD-binding site in TcdB1. Analysis of 206 TcdB variant sequences reveals a set of six residues within this receptor-binding site that defines a TFPI binding-associated haplotype (designated B4/B7) that is present in all TcdB4 members, a subset of TcdB7, and one member of TcdB2. Intragenic micro-recombination (IR) events have occurred around this receptor-binding region in TcdB7 and TcdB2 members, resulting in either TFPI- or FZD-binding capabilities. Introduction of B4/B7-haplotype residues into TcdB1 enables dual recognition of TFPI and FZDs. Finally, TcdB10 also recognizes TFPI, although it does not belong to the B4/B7 haplotype, and shows species selectivity: it recognizes TFPI of chicken and to a lesser degree mouse, but not human, dog, or cattle versions. These findings identify TFPI as a TcdB receptor and reveal IR-driven changes on receptor-specificity among TcdB variants.
The influence of recent and future climate change on spring Arctic cyclones
Authors: Parker Chelsea L. , Mooney Priscilla A. , Webster Melinda A. , Boisvert Linette N.
Published: November 2022

In recent decades, the Arctic has experienced rapid atmospheric warming and sea ice loss, with an ice-free Arctic projected by the end of this century. Cyclones are synoptic weather events that transport heat and moisture into the Arctic, and have complex impacts on sea ice, and the local and global climate. However, the effect of a changing climate on Arctic cyclone behavior remains poorly understood. This study uses high resolution (4 km), regional modeling techniques and downscaled global climate reconstructions and projections to examine how recent and future climatic changes alter cyclone behavior. Results suggest that recent climate change has not yet had an appreciable effect on Arctic cyclone characteristics. However, future sea ice loss and increasing surface temperatures drive large increases in the near-surface temperature gradient, sensible and latent heat fluxes, and convection during cyclones. The future climate can alter cyclone trajectories and increase and prolong intensity with greatly augmented wind speeds, temperatures, and precipitation. Such changes in cyclone characteristics could exacerbate sea ice loss and Arctic warming through positive feedbacks. The increasing extreme nature of these weather events has implications for local ecosystems, communities, and socio-economic activities.
Design of synthetic collagens that assemble into supramolecular banded fibers as a functional biomaterial testbed
Authors: Hu Jinyuan , Li Junhui , Jiang Jennifer , Wang Lingling , Roth Jonathan , McGuinness Kenneth N. , Baum Jean , Dai Wei , Sun Yao , Nanda Vikas , Xu Fei
Published: November 2022

Collagens are the most abundant proteins of the extracellular matrix, and the hierarchical folding and supramolecular assembly of collagens into banded fibers is essential for mediating cell-matrix interactions and tissue mechanics. Collagen extracted from animal tissues is a valuable commodity, but suffers from safety and purity issues, limiting its biomaterials applications. Synthetic collagen biomaterials could address these issues, but their construction requires molecular-level control of folding and supramolecular assembly into ordered banded fibers, comparable to those of natural collagens. Here, we show an innovative class of banded fiber-forming synthetic collagens that recapitulate the morphology and some biological properties of natural collagens. The synthetic collagens comprise a functional-driver module that is flanked by adhesive modules that effectively promote their supramolecular assembly. Multiscale simulations support a plausible molecular-level mechanism of supramolecular assembly, allowing precise design of banded fiber morphology. We also experimentally demonstrate that synthetic fibers stimulate osteoblast differentiation at levels comparable to natural collagen. This work thus deepens understanding of collagen biology and disease by providing a ready source of safe, functional biomaterials that bridge the current gap between the simplicity of peptide biophysical models and the complexity of in vivo animal systems.
Regiospecific α-methylene functionalisation of tertiary amines with alkynes via Au-catalysed concerted one-proton/two-electron transfer to O2
Authors: Yatabe Takafumi , Yamaguchi Kazuya
Published: November 2022

Regioselective transformations of tertiary amines, which are ubiquitously present in natural products and drugs, are important for the development of novel medicines. In particular, the oxidative α-C–H functionalisation of tertiary amines with nucleophiles via iminium cations is a promising approach because, theoretically, there is almost no limit to the type of amine and functionalisation. However, most of the reports on oxidative α-C–H functionalisations are limited to α-methyl-selective or non-selective reactions, despite the frequent appearance of α-methylene-substituted amines in pharmaceutical fields. Herein, we develop an unusual oxidative regiospecific α-methylene functionalisation of structurally diverse tertiary amines with alkynes to synthesise various propargylic amines using a catalyst comprising Zn salts and hydroxyapatite-supported Au nanoparticles. Thorough experimental investigations suggest that the unusual α-methylene regiospecificity is probably due to a concerted one-proton/two-electron transfer from amines to O2 on the Au nanoparticle catalyst, which paves the way to other α-methylene-specific functionalisations.
Symmetry-breaking in patch formation on triangular gold nanoparticles by asymmetric polymer grafting
Authors: Kim Ahyoung , Vo Thi , An Hyosung , Banerjee Progna , Yao Lehan , Zhou Shan , Kim Chansong , Milliron Delia J. , Glotzer Sharon C. , Chen Qian
Published: November 2022

Synthesizing patchy particles with predictive control over patch size, shape, placement and number has been highly sought-after for nanoparticle assembly research, but is fraught with challenges. Here we show that polymers can be designed to selectively adsorb onto nanoparticle surfaces already partially coated by other chains to drive the formation of patchy nanoparticles with broken symmetry. In our model system of triangular gold nanoparticles and polystyrene-b-polyacrylic acid patch, single- and double-patch nanoparticles are produced at high yield. These asymmetric single-patch nanoparticles are shown to assemble into self-limited patch‒patch connected bowties exhibiting intriguing plasmonic properties. To unveil the mechanism of symmetry-breaking patch formation, we develop a theory that accurately predicts our experimental observations at all scales—from patch patterning on nanoparticles, to the size/shape of the patches, to the particle assemblies driven by patch‒patch interactions. Both the experimental strategy and theoretical prediction extend to nanoparticles of other shapes such as octahedra and bipyramids. Our work provides an approach to leverage polymer interactions with nanoscale curved surfaces for asymmetric grafting in nanomaterials engineering.
A biomimetic ocular prosthesis system: emulating autonomic pupil and corneal reflections
Authors: Kim Seongchan , Choi Yoon Young , Kim Taewan , Kim Yong Min , Ho Dong Hae , Choi Young Jin , Roe Dong Gue , Lee Ju-Hee , Park Joongpill , Choi Ji-Woong , Kim Jeong Won , Park Jin-Hong , Jo Sae Byeok , Moon Hong Chul , Jeong Sohee , Cho Jeong Ho
Published: November 2022

The human light modulation response allows humans to perceive objects clearly by receiving the appropriate amount of light from the environment. This paper proposes a biomimetic ocular prosthesis system that mimics the human light modulation response capable of pupil and corneal reflections. First, photoinduced synaptic properties of the quantum dot embedded photonic synapse and its biosimilar signal transmission is confirmed. Subsequently, the pupillary light reflex is emulated by incorporating the quantum dot embedded photonic synapse, electrochromic device, and CMOS components. Moreover, a solenoid-based eyelid is connected to the pupillary light reflex system to emulate the corneal reflex. The proposed ocular prosthesis system represents a platform for biomimetic prosthesis that can accommodate an appropriate amount of stimulus by self-regulating the intensity of external stimuli.
Bidirectional and parallel relationships in macaque face circuit revealed by fMRI and causal pharmacological inactivation
Authors: Liu Ning , Behrmann Marlene , Turchi Janita N. , Avidan Galia , Hadj-Bouziane Fadila , Ungerleider Leslie G.
Published: November 2022

Although the presence of face patches in primate inferotemporal (IT) cortex is well established, the functional and causal relationships among these patches remain elusive. In two monkeys, muscimol was infused sequentially into each patch or pair of patches to assess their respective influence on the remaining IT face network and the amygdala, as determined using fMRI. The results revealed that anterior face patches required input from middle face patches for their responses to both faces and objects, while the face selectivity in middle face patches arose, in part, from top-down input from anterior face patches. Moreover, we uncovered a parallel fundal-lateral functional organization in the IT face network, supporting dual routes (dorsal-ventral) in face processing within IT cortex as well as between IT cortex and the amygdala. Our findings of the causal relationship among the face patches demonstrate that the IT face circuit is organized into multiple functional compartments.
Costimulation blockade in combination with IL-2 permits regulatory T cell sparing immunomodulation that inhibits autoimmunity
Authors: Wang Chun Jing , Petersone Lina , Edner Natalie M. , Heuts Frank , Ovcinnikovs Vitalijs , Ntavli Elisavet , Kogimtzis Alexandros , Fabri Astrid , Elfaki Yassin , Houghton Luke P. , Hosse Ralf J. , Schubert David A. , Frei Andreas P. , Ross Ellen M. , Walker Lucy S. K.
Published: November 2022

Blockade of CD28 costimulation with CTLA-4-Ig/Abatacept is used to dampen effector T cell responses in autoimmune and transplantation settings. However, a significant drawback of this approach is impaired regulatory T cell homeostasis that requires CD28 signaling. Therefore, strategies that restrict the effects of costimulation blockade to effector T cells would be advantageous. Here we probe the relative roles of CD28 and IL-2 in maintaining Treg. We find provision of IL-2 counteracts the regulatory T cell loss induced by costimulation blockade while minimally affecting the conventional T cell compartment. These data suggest that combining costimulation blockade with IL-2 treatment may selectively impair effector T cell responses while maintaining regulatory T cells. Using a mouse model of autoimmune diabetes, we show combined therapy supports regulatory T cell homeostasis and protects from disease. These findings are recapitulated in humanised mice using clinically relevant reagents and provide an exemplar for rational use of a second immunotherapy to offset known limitations of the first.
Structural dynamics of AAA + ATPase Drg1 and mechanism of benzo-diazaborine inhibition
Authors: Ma Chengying , Wu Damu , Chen Qian , Gao Ning
Published: November 2022

The type II AAA + ATPase Drg1 is a ribosome assembly factor, functioning to release Rlp24 from the pre-60S particle just exported from nucleus, and its activity in can be inhibited by a drug molecule diazaborine. However, molecular mechanisms of Drg1-mediated Rlp24 removal and diazaborine-mediated inhibition are not fully understood. Here, we report Drg1 structures in different nucleotide-binding and benzo-diazaborine treated states. Drg1 hexamers transits between two extreme conformations (planar or helical arrangement of protomers). By forming covalent adducts with ATP molecules in both ATPase domain, benzo-diazaborine locks Drg1 hexamers in a symmetric and non-productive conformation to inhibits both inter-protomer and inter-ring communication of Drg1 hexamers. We also obtained a substrate-engaged mutant Drg1 structure, in which conserved pore-loops form a spiral staircase to interact with the polypeptide through a sequence-independent manner. Structure-based mutagenesis data highlight the functional importance of the pore-loop, the D1-D2 linker and the inter-subunit signaling motif of Drg1, which share similar regulatory mechanisms with p97. Our results suggest that Drg1 may function as an unfoldase that threads a substrate protein within the pre-60S particle.
Cryo-EM reveals the architecture of the PELP1-WDR18 molecular scaffold
Authors: Gordon Jacob , Chapus Fleur L. , Viverette Elizabeth G. , Williams Jason G. , Deterding Leesa J. , Krahn Juno M. , Borgnia Mario J. , Rodriguez Joseph , Warren Alan J. , Stanley Robin E.
Published: November 2022

PELP1 (Proline-, Glutamic acid-, Leucine-rich protein 1) is a large scaffolding protein that functions in many cellular pathways including steroid receptor (SR) coactivation, heterochromatin maintenance, and ribosome biogenesis. PELP1 is a proto-oncogene whose expression is upregulated in many human cancers, but how the PELP1 scaffold coordinates its diverse cellular functions is poorly understood. Here we show that PELP1 serves as the central scaffold for the human Rix1 complex whose members include WDR18, TEX10, and SENP3. We reconstitute the mammalian Rix1 complex and identified a stable sub-complex comprised of the conserved PELP1 Rix1 domain and WDR18. We determine a 2.7 Å cryo-EM structure of the subcomplex revealing an interconnected tetrameric assembly and the architecture of PELP1’s signaling motifs, including eleven LxxLL motifs previously implicated in SR signaling and coactivation of Estrogen Receptor alpha (ERα) mediated transcription. However, the structure shows that none of these motifs is in a conformation that would support SR binding. Together this work establishes that PELP1 scaffolds the Rix1 complex, and association with WDR18 may direct PELP1’s activity away from SR coactivation.
Spatial genomics maps the structure, nature and evolution of cancer clones
Authors: Lomakin Artem , Svedlund Jessica , Strell Carina , Gataric Milana , Shmatko Artem , Rukhovich Gleb , Park Jun Sung , Ju Young Seok , Dentro Stefan , Kleshchevnikov Vitalii , Vaskivskyi Vasyl , Li Tong , Bayraktar Omer Ali , Pinder Sarah , Richardson Andrea L. , Santagata Sandro , Campbell Peter J. , Russnes Hege , Gerstung Moritz , Nilsson Mats , Yates Lucy R.
Published: November 2022

Genome sequencing of cancers often reveals mosaics of different subclones present in the same tumour1–3. Although these are believed to arise according to the principles of somatic evolution, the exact spatial growth patterns and underlying mechanisms remain elusive4,5. Here, to address this need, we developed a workflow that generates detailed quantitative maps of genetic subclone composition across whole-tumour sections. These provide the basis for studying clonal growth patterns, and the histological characteristics, microanatomy and microenvironmental composition of each clone. The approach rests on whole-genome sequencing, followed by highly multiplexed base-specific in situ sequencing, single-cell resolved transcriptomics and dedicated algorithms to link these layers. Applying the base-specific in situ sequencing workflow to eight tissue sections from two multifocal primary breast cancers revealed intricate subclonal growth patterns that were validated by microdissection. In a case of ductal carcinoma in situ, polyclonal neoplastic expansions occurred at the macroscopic scale but segregated within microanatomical structures. Across the stages of ductal carcinoma in situ, invasive cancer and lymph node metastasis, subclone territories are shown to exhibit distinct transcriptional and histological features and cellular microenvironments. These results provide examples of the benefits afforded by spatial genomics for deciphering the mechanisms underlying cancer evolution and microenvironmental ecology.
Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir
Authors: Iketani Sho , Mohri Hiroshi , Culbertson Bruce , Hong Seo Jung , Duan Yinkai , Luck Maria I. , Annavajhala Medini K. , Guo Yicheng , Sheng Zizhang , Uhlemann Anne-Catrin , Goff Stephen P. , Sabo Yosef , Yang Haitao , Chavez Alejandro , Ho David D.
Published: November 2022

Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been demonstrated to be clinically useful against COVID-19 (refs. 1,2). However, because SARS-CoV-2 has evolved to become resistant to other therapeutic modalities3–9, there is a concern that the same could occur for nirmatrelvir. Here we examined this possibility by in vitro passaging of SARS-CoV-2 in nirmatrelvir using two independent approaches, including one on a large scale. Indeed, highly resistant viruses emerged from both and their sequences showed a multitude of 3CL protease mutations. In the experiment peformed with many replicates, 53 independent viral lineages were selected with mutations observed at 23 different residues of the enzyme. Nevertheless, several common mutational pathways to nirmatrelvir resistance were preferred, with a majority of the viruses descending from T21I, P252L or T304I as precursor mutations. Construction and analysis of 13 recombinant SARS-CoV-2 clones showed that these mutations mediated only low-level resistance, whereas greater resistance required accumulation of additional mutations. E166V mutation conferred the strongest resistance (around 100-fold), but this mutation resulted in a loss of viral replicative fitness that was restored by compensatory changes such as L50F and T21I. Our findings indicate that SARS-CoV-2 resistance to nirmatrelvir does readily arise via multiple pathways in vitro, and the specific mutations observed herein form a strong foundation from which to study the mechanism of resistance in detail and to inform the design of next-generation protease inhibitors.
Moving beyond response times with accessible measures of manual dynamics
Authors: Smith Katie Ann , Morrison Samara , Henderson Annette M. E. , Erb Christopher D.
Published: November 2022

Button-press measures of response time (RT) and accuracy have long served a central role in psychological research. However, RT and accuracy provide limited insight into how cognitive processes unfold over time. To address this limitation, researchers have used hand-tracking techniques to investigate how cognitive processes unfold over the course of a response, are modulated by recent experience, and function across the lifespan. Despite the efficacy of these techniques for investigating a wide range of psychological phenomena, widespread adoption of hand-tracking techniques within the field is hindered by a range of factors, including equipment costs and the use of specialized software. Here, we demonstrate that the behavioral dynamics previously observed with specialized motion-tracking equipment in an Eriksen flanker task can be captured with an affordable, portable, and easy-to-assemble response box. Six-to-eight-year-olds and adults (N = 90) completed a computerized version of the flanker task by pressing and holding a central button until a stimulus array appeared. Participants then responded by releasing the central button and reaching to press one of two response buttons. This method allowed RT to be separated into initiation time (when the central button was released) and movement time (time elapsed between initiation and completion of the response). Consistent with previous research using motion-tracking techniques, initiation times and movement times revealed distinct patterns of effects across trials and between age groups, indicating that the method used in the current study presents a simple solution for researchers from across the psychological and brain sciences looking to move beyond RTs.
Neuromechanical control of impact absorption during induced lower limb loading in individuals post-stroke
Authors: Shen Keng-Hung , Prajapati Sunil K. , Borrelli James , Gray Vicki L. , Westlake Kelly P. , Rogers Mark W. , Hsiao Hao-Yuan
Published: November 2022

Decreased loading of the paretic lower limb and impaired weight transfer between limbs negatively impact balance control and forward progression during gait in individuals post-stroke. However, the biomechanical and neuromuscular control mechanisms underlying such impaired limb loading remain unclear, partly due to their tendency of avoiding bearing weight on the paretic limb during voluntary movement. Thus, an approach that forces individuals to more fully and rapidly load the paretic limb has been developed. The primary purpose of this study was to compare the neuromechanical responses at the ankle and knee during externally induced limb loading in people with chronic stroke versus able-bodied controls, and determine whether energy absorption capacity, measured during induced limb loading of the paretic limb, was associated with walking characteristics in individuals post-stroke. Results revealed reduced rate of energy absorption and dorsiflexion velocity at the ankle joint during induced limb loading in both the paretic and non-paretic side in individuals post-stroke compared to healthy controls. The co-contraction index was higher in the paretic ankle and knee joints compared to the non-paretic side. In addition, the rate of energy absorption at the paretic ankle joint during the induced limb loading was positively correlated with maximum walking speed and negatively correlated with double limb support duration. These findings demonstrated that deficits in ankle dorsiflexion velocity may limit the mechanical energy absorption capacity of the joint and thereby affect the lower limb loading process during gait following stroke.
Machine learning algorithm for estimating karst rocky desertification in a peak-cluster depression basin in southwest Guangxi, China
Authors: Zhang Yali , Tian Yichao , Li Ying , Wang Donghua , Tao Jin , Yang Yongwei , Lin Junliang , Zhang Qiang , Wu Luhua
Published: November 2022

Karst rocky desertification (KRD) has become one of the most serious ecological and environmental problems in karst areas. At present, mapping KRD with a high accuracy and on a large scale is still a difficult problem in the control of KRD. In this study, a random forest (RF) based on maximum information coefficient and correlation coefficient feature selection is proposed to predict KRD. Nine predictors stood out as feature factors to estimate KRD. Rock exposure was the most important predictor, followed by fractional vegetation cover for the prediction of KRD processes. The kappa and classification accuracy indexes were to evaluate the performance of the model. We recorded overall accuracy rate and kappa index values of 94.7% and 0.92 for the testing datasets respectively. The RF model was then used to predict the KRD in 2001, 2011, 2016, and 2020, and it was found that the KRD in the study area has exhibited a positive trend of improvement. Therefore, the use of multisource remote sensing data combined with the RF model can obtain better prediction results of KRD, thereby providing a new idea for large-scale estimation of the KRD in peak-cluster depression.
Plasmidome in mcr-1 harboring carbapenem-resistant enterobacterales isolates from human in Thailand
Authors: Boueroy Parichart , Wongsurawat Thidathip , Jenjaroenpun Piroon , Chopjitt Peechanika , Hatrongjit Rujirat , Jittapalapong Sathaporn , Kerdsin Anusak
Published: November 2022

The emergence of the mobile colistin-resistance genes mcr-1 has attracted significant attention worldwide. This study aimed to investigate the genetic features of mcr-1-carrying plasmid among carbapenem-resistant Enterobacterales (CRE) isolates and the potential genetic basis governing transmission. Seventeen mcr-harboring isolates were analyzed based on whole genome sequencing using short-read and long-read platforms. All the mcr-1-carrying isolates could be conjugatively transferred into a recipient Escherichia coli UB1637. Among these 17 isolates, mcr-1 was located on diverse plasmid Inc types, consisting of IncX4 (11/17; 64.7%), IncI2 (4/17; 23.53%), and IncHI/IncN (2/17; 11.76%). Each of these exhibited remarkable similarity in the backbone set that is responsible for plasmid replication, maintenance, and transfer, with differences being in the upstream and downstream regions containing mcr-1. The IncHI/IncN type also carried other resistance genes (blaTEM-1B or blaTEM-135). The mcr-1-harboring IncX4 plasmids were carried in E. coli ST410 (7/11; 63.6%) and ST10 (1/11; 9.1%) and Klebsiella pneumoniae ST15 (1/11; 9.1%), ST336 (1/11; 9.1%), and ST340 (1/11; 9.1%). The IncI2-type plasmid was harbored in E. coli ST3052 (1/4; 25%) and ST1287 (1/4; 25%) and in K. pneumoniae ST336 (2/4; 50%), whereas IncHI/IncN were carried in E. coli ST6721 (1/2; 50%) and new ST (1/2; 50%). The diverse promiscuous plasmids may facilitate the spread of mcr-1 among commensal E. coli or K. pneumoniae strains in patients. These results can provide information for a surveillance system and infection control for dynamic tracing.
Driven translocation of a semiflexible polymer through a conical channel in the presence of attractive surface interactions
Authors: Sharma Andri , Kapri Rajeev , Chaudhuri Abhishek
Published: November 2022

We study the translocation of a semiflexible polymer through a conical channel with attractive surface interactions and a driving force which varies spatially inside the channel. Using the results of the translocation dynamics of a flexible polymer through an extended channel as control, we first show that the asymmetric shape of the channel gives rise to non-monotonic features in the total translocation time as a function of the apex angle of the channel. The waiting time distributions of individual monomer beads inside the channel show unique features strongly dependent on the driving force and the surface interactions. Polymer stiffness results in longer translocation times for all angles of the channel. Further, non-monotonic features in the translocation time as a function of the channel angle changes substantially as the polymer becomes stiffer, which is reflected in the changing features of the waiting time distributions. We construct a free energy description of the system incorporating entropic and energetic contributions in the low force regime to explain the simulation results.
In silico comparative genomic analysis unravels a new candidate protein arsenal specifically associated with Fusarium oxysporum f. sp. albedinis pathogenesis
Authors: Ayada Hafida , Dhioui Boutayna , Mazouz Hamid , El harrak Abdelhay , Jaiti Fatima , Ouhmidou Bouchra , Diouri Mohammed , Moumni Mohieddine
Published: November 2022

Fusarium oxysporum f. sp albedinis (Foa) is a devastating fungus of date palms. To unravel the genetic characteristics associated with its pathogenesis, the two available genomes of Foa 133 and Foa 9 were compared with 49 genomes of 29 other pathogenic formae speciales belonging to Fusarium oxysporum species complex (FOSC). Foa 133 and Foa 9 have genomes of 56.23 Mb and 65.56 Mb with 17460 and 19514 putative coding genes. Of these genes, 30% lack functional annotation with no similarity to characterized proteins. The remaining genes were involved in pathways essential to the fungi's life and their adaptation. Foa secretome analysis revealed that both Foa strains possess an expanded number of secreted effectors (3003 in Foa 133 and 2418 in Foa 9). Those include effectors encoded by Foa unique genes that are involved in Foa penetration (Egh16-like family), host defense mechanisms suppression (lysM family) and pathogen protection (cysteine-rich protein family). The accessory protein SIX6, which induces plant cell death, was also predicted in Foa. Further analysis of secreted CAZymes revealed an arsenal of enzymes involved in plant cell wall degradation. This arsenal includes an exclusively Foa-specific CAZyme (GH5-7). Transcription factors and membrane transporters (MFS) involved in fungicide efflux have been predicted in Foa, in addition to a variety of secondary metabolites. These comprise mycotoxins as well as chrysogin, the latter provides Foa with resistance against adverse environmental conditions. Our results revealed new Foa proteins that could be targeted in future research in order to manage Bayoud disease.
Establishment of a model for predicting the outcome of induced labor in full-term pregnancy based on machine learning algorithm
Authors: Hu Tingting , Du Sisi , Li Xiaoyan , Yang Fang , Zhang Shanshan , Yi Jingjing , Xiao Birong , Li Tingting , He Lin
Published: November 2022

To evaluate and establish a prediction model of the outcome of induced labor based on machine learning algorithm. This was a cross-sectional design. The subjects were divided into primipara and multipara, and the risk factors for the outcomes of induced labor were assessed by multifactor logistic regression analysis. The outcome model of labor induced with oxytocin (OT) was constructed based on the four machine learning algorithms, including AdaBoost, logistic regression, naive Bayes classifier, and support vector machine. Factors, such as accuracy, recall, precision, F1 value, and receiver operating characteristic curve, were used to evaluate the prediction performance of the model, and the clinical application of the model was verified. A total of 907 participants were included in this study. Logistic regression algorithm obtained better results in both primipara and multipara groups compared to the other three models. The accuracy of the model for the prediction of “successful induction of labor” was 94.24% and 96.55%, and that of “failed induction of labor” was 65.00% and 66.67% in the primipara and the multipara groups, respectively. This study established a prediction model of OT-induced labor based on the Logistic regression algorithm, with rapid response, high accuracy, and strong extrapolation, which was critical for obstetric clinical nursing.
Achieving of high-diet-fiber barley via managing fructan hydrolysis
Authors: Fei Mingliang , Jin Yunkai , Hu Jia , Dotsenko Gleb , Ruan Ying , Liu Chunlin , Seisenbaeva Gulaim , Andersson Annica A. M. , Andersson Roger , Sun Chuanxin
Published: November 2022

High fructan content in the grain of cereals is an important trait in agriculture such as environmental resilience and dietary fiber food production. To understand the mechanism in determining final grain fructan content and achieve high fructan cereal, a cross breeding strategy based on fructan synthesis and hydrolysis activities was set up and have achieved barley lines with 11.8% storage fructan in the harvested grain. Our study discovered that high activity of fructan hydrolysis at later grain developmental stage leads to the low fructan content in mature seeds, simultaneously increasing fructan synthesis at early stage and decreasing fructan hydrolysis at later stage through crossing breeding is an efficient way to elevate grain diet-fiber content. A good correlation between fructan and beta glucans was also discovered with obvious interest. Field trials showed that the achieved high fructan barley produced over seven folds higher fructan content than control barley and pull carbon-flux to fructan through decreasing fructan hydrolysis without disruption starch synthesis will probably not bring yield deficiency.
The first space-filling polyhedrons of polymer cubic cells originated from Weaire-Phelan structure created by polymerization induced phase separation
Authors: Naga Naofumi , Jinno Masumi , Wang Yuting , Nakano Tamaki
Published: November 2022

The Weaire–Phelan structure is a three-dimensional structure composed of two different polyhedra having the same volume, i.e., pyritohedron and truncated hexagonal trapezohedron. It was proposed by Weaire and Phelan in 1993 as a solution of the Kelvin problem of filling space with no gaps with cells of minimum surface area and equal volume. It was found in physical systems including liquid foam and a metal alloy while it has never been constructed as organic materials. We report herewith the first polymeric Weaire–Phelan structure constructed through phase-separation of a single polymer species that is synthesized by simple polyaddition between tetrakis(3-mercaptopropionate) and 1,6-diisocyanatohexane. The structure has the order of micrometers and is amorphous unlike reported crystal structures similar to the Weaire–Phelan structure.
Loss of SATB2 expression correlates with cytokeratin 7 and PD-L1 tumor cell positivity and aggressiveness in colorectal cancer
Authors: Hrudka Jan , Matěj Radoslav , Nikov Andrej , Tomyak Igor , Fišerová Hana , Jelínková Karolína , Waldauf Petr
Published: November 2022

Colorectal carcinoma (CRC) is a disease that causes significant morbidity and mortality worldwide. To improve treatment, new biomarkers are needed to allow better patient risk stratification in terms of prognosis. This study aimed to clarify the prognostic significance of colonic-specific transcription factor special AT-rich sequence-binding protein 2 (SATB2), cytoskeletal protein cytokeratin 7 (CK7), and immune checkpoint molecule programmed death-ligand 1 (PD-L1). We analyzed a cohort of 285 patients with surgically treated CRC for quantitative associations among the three markers and five traditional prognostic indicators (i.e., tumor stage, histological grade, variant morphology, laterality, and mismatch-repair/MMR status). The results showed that loss of SATB2 expression had significant negative prognostic implications relative to overall survival (OS) and cancer-specific survival (CSS), significantly shortened 5 years OS and CSS and 10 years CSS in patients with CRC expressing CK7, and borderline insignificantly shortened OS in patients with PD-L1 + CRC. PD-L1 showed a significant negative impact in cases with strong expression (membranous staining in 50–100% of tumor cells). Loss of SATB2 was associated with CK7 expression, advanced tumor stage, mucinous or signet ring cell morphology, high grade, right-sided localization but was borderline insignificant relative to PD-L1 expression. CK7 expression was associated with high grade and SATB2 loss. Additionally, a separate analysis of 248 neoadjuvant therapy-naïve cases was performed with mostly similar results. The loss of SATB2 and CK7 expression were significant negative predictors in the multivariate analysis adjusted for associated parameters and patient age. In summary, loss of SATB2 expression and gain of CK7 and strong PD-L1 expression characterize an aggressive phenotype of CRC.