bluuebunny/crossref_metadata_2025 huggingface dataset:
Acentrosomal spindles assemble from branching microtubule nucleation near chromosomes in Xenopus laevis egg extract
Authors: Gouveia Bernardo , Setru Sagar U. , King Matthew R. , Hamlin Aaron , Stone Howard A. , Shaevitz Joshua W. , Petry Sabine
Published: June 2023

Microtubules are generated at centrosomes, chromosomes, and within spindles during cell division. Whereas microtubule nucleation at the centrosome is well characterized, much remains unknown about where, when, and how microtubules are nucleated at chromosomes. To address these questions, we reconstitute microtubule nucleation from purified chromosomes in meiotic Xenopus egg extract and find that chromosomes alone can form spindles. We visualize microtubule nucleation near chromosomes using total internal reflection fluorescence microscopy to find that this occurs through branching microtubule nucleation. By inhibiting molecular motors, we find that the organization of the resultant polar branched networks is consistent with a theoretical model where the effectors for branching nucleation are released by chromosomes, forming a concentration gradient that spatially biases branching microtbule nucleation. In the presence of motors, these branched networks are ultimately organized into functional spindles, where the number of emergent spindle poles scales with the number of chromosomes and total chromatin area.
CAJAL enables analysis and integration of single-cell morphological data using metric geometry
Authors: Govek Kiya W. , Nicodemus Patrick , Lin Yuxuan , Crawford Jake , Saturnino Artur B. , Cui Hannah , Zoga Kristi , Hart Michael P. , Camara Pablo G.
Published: June 2023

High-resolution imaging has revolutionized the study of single cells in their spatial context. However, summarizing the great diversity of complex cell shapes found in tissues and inferring associations with other single-cell data remains a challenge. Here, we present CAJAL, a general computational framework for the analysis and integration of single-cell morphological data. By building upon metric geometry, CAJAL infers cell morphology latent spaces where distances between points indicate the amount of physical deformation required to change the morphology of one cell into that of another. We show that cell morphology spaces facilitate the integration of single-cell morphological data across technologies and the inference of relations with other data, such as single-cell transcriptomic data. We demonstrate the utility of CAJAL with several morphological datasets of neurons and glia and identify genes associated with neuronal plasticity inC. elegans. Our approach provides an effective strategy for integrating cell morphology data into single-cell omics analyses.
Molecular choreography of primer synthesis by the eukaryotic Pol α-primase
Authors: Yuan Zuanning , Georgescu Roxana , Li Huilin , O’Donnell Michael E.
Published: June 2023

The eukaryotic polymerase α (Pol α) synthesizes an RNA-DNA hybrid primer of 20–30 nucleotides. Pol α is composed of Pol1, Pol12, Primase 1 (Pri1), and Pri2. Pol1 and Pri1 contain the DNA polymerase and RNA primase activities, respectively. It has been unclear how Pol α hands over an RNA primer from Pri1 to Pol1 for DNA primer extension, and how the primer length is defined. Here we report the cryo-EM analysis of yeast Pol α in the apo, primer initiation, primer elongation, RNA primer hand-off from Pri1 to Pol1, and DNA extension states, revealing a series of very large movements. We reveal a critical point at which Pol1-core moves to take over the 3’-end of the RNA from Pri1. DNA extension is limited by a spiral motion of Pol1-core. Since both Pri1 and Pol1-core are flexibly attached to a stable platform, primer growth produces stress that limits the primer length.
A phase Ib trial of pembrolizumab plus paclitaxel or flat-dose capecitabine in 1st/2nd line metastatic triple-negative breast cancer
Authors: Page David B. , Pucilowska Joanna , Chun Brie , Kim Isaac , Sanchez Katherine , Moxon Nicole , Mellinger Staci , Wu Yaping , Koguchi Yoshinobu , Conrad Valerie , Redmond William L. , Martel Maritza , Sun Zhaoyu , Campbell Mary B. , Conlin Alison , Acheson Anupama , Basho Reva , McAndrew Philomena , El-Masry Mary , Park Dorothy , Bennetts Laura , Seitz Robert S. , Nielsen Tyler J. , McGregor Kimberly , Rajamanickam Venkatesh , Bernard Brady , Urba Walter J. , McArthur Heather L.
Published: June 2023

Chemoimmunotherapy with anti-programmed cell death 1/ligand 1 and cytotoxic chemotherapy is a promising therapeutic modality for women with triple-negative breast cancer, but questions remain regarding optimal chemotherapy backbone and biomarkers for patient selection. We report final outcomes from a phase Ib trial evaluating pembrolizumab (200 mg IV every 3 weeks) with either weekly paclitaxel (80 mg/m2 weekly) or flat-dose capecitabine (2000 mg orally twice daily for 7 days of every 14-day cycle) in the 1st/2nd line setting. The primary endpoint is safety (receipt of 2 cycles without grade III/IV toxicities requiring discontinuation or ≥21-day delays). The secondary endpoint is efficacy (week 12 objective response). Exploratory aims are to characterize immunologic effects of treatment over time, and to evaluate novel biomarkers. The trial demonstrates that both regimens meet the pre-specified safety endpoint (paclitaxel: 87%; capecitabine: 100%). Objective response rate is 29% for pembrolizumab/paclitaxel (n = 4/13, 95% CI: 10–61%) and 43% for pembrolizumab/capecitabine (n = 6/14, 95% CI: 18–71%). Partial responses are observed in two subjects with chemo-refractory metaplastic carcinoma (both in capecitabine arm). Both regimens are associated with significant peripheral leukocyte contraction over time. Response is associated with clinical PD-L1 score, non-receipt of prior chemotherapy, and the H&E stromal tumor-infiltrating lymphocyte score, but also by a novel 27 gene IO score and spatial biomarkers (lymphocyte spatial skewness). In conclusion, pembrolizumab with paclitaxel or capecitabine is safe and clinically active. Both regimens are lymphodepleting, highlighting the competing immunostimulatory versus lymphotoxic effects of cytotoxic chemotherapy. Further exploration of the IO score and spatial TIL biomarkers is warranted. The clinical trial registration is NCT02734290.
Photoexcitation induced magnetic phase transition and spin dynamics in antiferromagnetic MnPS3 monolayer
Authors: Gao Yinlu , Jiang Xue , Qiu Zhiyong , Zhao Jijun
Published: June 2023

Antiferromagnetic spin dynamics is the key issue to develop spintronic devices. We adopt ab initio nonadiabatic molecular dynamics with spin–orbit-coupling (SOC) to investigate photoinduced spin dynamics in an antiferromagnetic semiconductor MnPS3 monolayer. Optical doping triggers MnPS3 from Néel antiferromagnetic to ferromagnetic phase at an experimentally achievable electron–hole pair density of 1.11 × 1014 cm−2. This phase transition can be ascribed to the light-induced mid-gap states of S-p orbitals, which lower the electron excitation energy and strengthen the SOC effect between S-p and Mn-d orbitals. The excited S-p electrons first decay to the mid-gap states due to p–p electron–phonon-coupling and then relax to the spin-down Mn-d orbitals via SOC. Such a dramatic relaxation process prolongs the photogenerated carrier lifetime up to 648 fs, providing an explanation for the unusual optoelectronic performance of MnPS3. The reversible switching of magnetic order via optical means gives an important clue for information storage and highly efficient photocatalysts utilizing antiferromagnetic semiconductors.
Effect of gravity on the spreading of a droplet deposited by liquid needle deposition technique
Authors: Baldygin Aleksey , Ahmed Abrar , Baily Ryan , Ismail Md Farhad , Khan Muhammed , Rodrigues Nigel , Salehi Ali-Reza , Ramesh Megnath , Bhattacharya Sanjay , Willers Thomas , Gowanlock Derek , Waghmare Prashant R.
Published: June 2023

This study represents an experimental investigation, complemented with a mathematical model, to decipher the effect of gravity on the spreading dynamics of a water droplet. For the theoretical discussion, an overall energy balance approach is adopted to explain the droplet spreading under both microgravity (μg) and terrestrial gravity condition. Besides explaining the mechanism of the droplet spreading under microgravity condition achieved during the parabolic flight, a technique with a detailed experimental set-up has also been developed for the successful deposition of droplet. A rational understanding is formulated through experimental investigation and theoretical analysis, which allows us to distinguish the transient variation of the spreading of a droplet, between microgravity and terrestrial gravity condition. The spreading of the droplet is predicted by the non-linear overall energy balance equation, which accounts for the operating parameters in the form of non-dimensional groups like Reynolds number ($${{{\rm{Re}}}}$$
Re
), Weber number (We) and Bond number (Bo). To distinctly identify the difference in the drop spreading at terrestrial and microgravity conditions, the Bo with transient gravitational field obtained through the on-board accelerometer is considered. The obtained theoretical results are further corroborated by experimental results which are obtained from the parabolic flight.
Understanding biofouling and contaminant accretion on submerged marine structures
Authors: Vuong Paton , McKinley Allan , Kaur Parwinder
Published: June 2023

Fouling of maritime infrastructure is pervasive due to abundant biological and chemical activity within the oceanic environment. Marine biofilms and their successional growths are prevalent issues in biofouling, but current industrial and research-based analyses often do not provide a holistic view of the fouling biodiversity. Cathodic protection is a longstanding system safeguarding infrastructure from the corrosive marine environment, but limited studies on interactions between biological growth and cathodic activity have been conducted in the context of marine fouling. This review identifies knowledge gaps in the understanding of marine fouling and highlights approaches to better direct development of effective anti-fouling measures.
Entropic repulsion of cholesterol-containing layers counteracts bioadhesion
Authors: Friedrichs Jens , Helbig Ralf , Hilsenbeck Julia , Pandey Prithvi Raj , Sommer Jens-Uwe , Renner Lars David , Pompe Tilo , Werner Carsten
Published: June 2023

Control of adhesion is a striking feature of living matter that is of particular interest regarding technological translation1–3. We discovered that entropic repulsion caused by interfacial orientational fluctuations of cholesterol layers restricts protein adsorption and bacterial adhesion. Moreover, we found that intrinsically adhesive wax ester layers become similarly antibioadhesive when containing small quantities (under 10 wt%) of cholesterol. Wetting, adsorption and adhesion experiments, as well as atomistic simulations, showed that repulsive characteristics depend on the specific molecular structure of cholesterol that encodes a finely balanced fluctuating reorientation at the interface of unconstrained supramolecular assemblies: layers of cholesterol analogues differing only in minute molecular variations showed markedly different interfacial mobility and no antiadhesive effects. Also, orientationally fixed cholesterol layers did not resist bioadhesion. Our insights provide a conceptually new physicochemical perspective on biointerfaces and may guide future material design in regulation of adhesion.
Signalling by senescent melanocytes hyperactivates hair growth
Authors: Wang Xiaojie , Ramos Raul , Phan Anne Q. , Yamaga Kosuke , Flesher Jessica L. , Jiang Shan , Oh Ji Won , Jin Suoqin , Jahid Sohail , Kuan Chen-Hsiang , Nguyen Truman Kt , Liang Heidi Y. , Shettigar Nitish Udupi , Hou Renzhi , Tran Kevin H. , Nguyen Andrew , Vu Kimberly N. , Phung Jennie L. , Ingal Jonard P. , Levitt Katelyn M. , Cao Xiaoling , Liu Yingzi , Deng Zhili , Taguchi Nobuhiko , Scarfone Vanessa M. , Wang Guangfang , Paolilli Kara Nicole , Wang Xiaoyang , Guerrero-Juarez Christian F. , Davis Ryan T. , Greenberg Elyse Noelani , Ruiz-Vega Rolando , Vasudeva Priya , Murad Rabi , Widyastuti Lily Halida Putri , Lee Hye-Lim , McElwee Kevin J. , Gadeau Alain-Pierre , Lawson Devon A. , Andersen Bogi , Mortazavi Ali , Yu Zhengquan , Nie Qing , Kunisada Takahiro , Karin Michael , Tuckermann Jan , Esko Jeffrey D. , Ganesan Anand K. , Li Ji , Plikus Maksim V.
Published: June 2023

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.
Injury prevents Ras mutant cell expansion in mosaic skin
Authors: Gallini Sara , Annusver Karl , Rahman Nur-Taz , Gonzalez David G. , Yun Sangwon , Matte-Martone Catherine , Xin Tianchi , Lathrop Elizabeth , Suozzi Kathleen C. , Kasper Maria , Greco Valentina
Published: June 2023

Healthy skin is a mosaic of wild-type and mutant clones1,2. Although injury can cooperate with mutated Ras family proteins to promote tumorigenesis3–12, the consequences in genetically mosaic skin are unknown. Here we show that after injury, wild-type cells suppress aberrant growth induced by oncogenic Ras. HrasG12V/+ and KrasG12D/+ cells outcompete wild-type cells in uninjured, mosaic tissue but their expansion is prevented after injury owing to an increase in the fraction of proliferating wild-type cells. Mechanistically, we show that, unlike HrasG12V/+ cells, wild-type cells respond to autocrine and paracrine secretion of EGFR ligands, and this differential activation of the EGFR pathway explains the competitive switch during injury repair. Inhibition of EGFR signalling via drug or genetic approaches diminishes the proportion of dividing wild-type cells after injury, leading to the expansion of HrasG12V/+ cells. Increased proliferation of wild-type cells via constitutive loss of the cell cycle inhibitor p21 counteracts the expansion of HrasG12V/+ cells even in the absence of injury. Thus, injury has a role in switching the competitive balance between oncogenic and wild-type cells in genetically mosaic skin.
Origin and evolutionary malleability of T cell receptor α diversity
Authors: Giorgetti Orlando B. , O’Meara Connor P. , Schorpp Michael , Boehm Thomas
Published: June 2023

Lymphocytes of vertebrate adaptive immune systems acquired the capability to assemble, from split genes in the germline, billions of functional antigen receptors1–3. These receptors show specificity; unlike the broadly tuned receptors of the innate system, antibodies (Ig) expressed by B cells, for instance, can accurately distinguish between the two enantiomers of organic acids4, whereas T cell receptors (TCRs) reliably recognize single amino acid replacements in their peptide antigens5. In developing lymphocytes, antigen receptor genes are assembled from a comparatively small set of germline-encoded genetic elements in a process referred to as V(D)J recombination6,7. Potential self-reactivity of some antigen receptors arising from the quasi-random somatic diversification is suppressed by several robust control mechanisms8–12. For decades, scientists have puzzled over the evolutionary origin of somatically diversifying antigen receptors13–16. It has remained unclear how, at the inception of this mechanism, immunologically beneficial expanded receptor diversity was traded against the emerging risk of destructive self-recognition. Here we explore the hypothesis that in early vertebrates, sequence microhomologies marking the ends of recombining elements became the crucial targets of selection determining the outcome of non-homologous end joining-based repair of DNA double-strand breaks generated during RAG-mediated recombination. We find that, across the main clades of jawed vertebrates, TCRα repertoire diversity is best explained by species-specific extents of such sequence microhomologies. Thus, selection of germline sequence composition of rearranging elements emerges as a major factor determining the degree of diversity of somatically generated antigen receptors.
Single-cell quantification of ribosome occupancy in early mouse development
Authors: Ozadam Hakan , Tonn Tori , Han Crystal M. , Segura Alia , Hoskins Ian , Rao Shilpa , Ghatpande Vighnesh , Tran Duc , Catoe David , Salit Marc , Cenik Can
Published: June 2023

Translation regulation is critical for early mammalian embryonic development1. However, previous studies had been restricted to bulk measurements2, precluding precise determination of translation regulation including allele-specific analyses. Here, to address this challenge, we developed a novel microfluidic isotachophoresis (ITP) approach, named RIBOsome profiling via ITP (Ribo-ITP), and characterized translation in single oocytes and embryos during early mouse development. We identified differential translation efficiency as a key mechanism regulating genes involved in centrosome organization and N6-methyladenosine modification of RNAs. Our high-coverage measurements enabled, to our knowledge, the first analysis of allele-specific ribosome engagement in early development. These led to the discovery of stage-specific differential engagement of zygotic RNAs with ribosomes and reduced translation efficiency of transcripts exhibiting allele-biased expression. By integrating our measurements with proteomics data, we discovered that ribosome occupancy in germinal vesicle-stage oocytes is the predominant determinant of protein abundance in the zygote. The Ribo-ITP approach will enable numerous applications by providing high-coverage and high-resolution ribosome occupancy measurements from ultra-low input samples including single cells.
Site specific N- and O-glycosylation mapping of the spike proteins of SARS-CoV-2 variants of concern
Authors: Shajahan Asif , Pepi Lauren E. , Kumar Bhoj , Murray Nathan B. , Azadi Parastoo
Published: June 2023

The glycosylation on the spike (S) protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, modulates the viral infection by altering conformational dynamics, receptor interaction and host immune responses. Several variants of concern (VOCs) of SARS-CoV-2 have evolved during the pandemic, and crucial mutations on the S protein of the virus have led to increased transmissibility and immune escape. In this study, we compare the site-specific glycosylation and overall glycomic profiles of the wild type Wuhan-Hu-1 strain (WT) S protein and five VOCs of SARS-CoV-2: Alpha, Beta, Gamma, Delta and Omicron. Interestingly, both N- and O-glycosylation sites on the S protein are highly conserved among the spike mutant variants, particularly at the sites on the receptor-binding domain (RBD). The conservation of glycosylation sites is noteworthy, as over 2 million SARS-CoV-2 S protein sequences have been reported with various amino acid mutations. Our detailed profiling of the glycosylation at each of the individual sites of the S protein across the variants revealed intriguing possible association of glycosylation pattern on the variants and their previously reported infectivity. While the sites are conserved, we observed changes in the N- and O-glycosylation profile across the variants. The newly emerged variants, which showed higher resistance to neutralizing antibodies and vaccines, displayed a decrease in the overall abundance of complex-type glycans with both fucosylation and sialylation and an increase in the oligomannose-type glycans across the sites. Among the variants, the glycosylation sites with significant changes in glycan profile were observed at both the N-terminal domain and RBD of S protein, with Omicron showing the highest deviation. The increase in oligomannose-type happens sequentially from Alpha through Delta. Interestingly, Omicron does not contain more oligomannose-type glycans compared to Delta but does contain more compared to the WT and other VOCs. O-glycosylation at the RBD showed lower occupancy in the VOCs in comparison to the WT. Our study on the sites and pattern of glycosylation on the SARS-CoV-2 S proteins across the VOCs may help to understand how the virus evolved to trick the host immune system. Our study also highlights how the SARS-CoV-2 virus has conserved both N- and O- glycosylation sites on the S protein of the most successful variants even after undergoing extensive mutations, suggesting a correlation between infectivity/ transmissibility and glycosylation.
Terfezia boudieri and Terfezia claveryi inhibit the LPS/IFN-γ-mediated inflammation in RAW 264.7 macrophages through an Nrf2-independent mechanism
Authors: Dawood Abdelhameed S. , Sedeek Mohamed S. , Farag Mohamed A. , Abdelnaser Anwar
Published: June 2023

Desert truffles have been used as traditional treatments for numerous inflammatory disorders. However, the molecular mechanisms underlying their anti-inflammatory effects in RAW 264.7 macrophages have yet to be fully elucidated. The present study investigated the anti-inflammatory activities of two main desert truffles, Terfezia boudieri and T. claveryi, and the underlying mechanisms associated with their anti-inflammatory activities in RAW 264.7 macrophages stimulated with lipopolysaccharide/interferon-gamma (LPS/IFN-γ). Our results demonstrated that treatment with T. boudieri and T. claveryi extracts effectively suppressed the inflammatory response in LPS/IFN-γ-stimulated RAW 264.7 macrophages. Specifically, T. boudieri extract was found to reduce the production of nitric oxide and inhibit the expression of various pro-inflammatory markers, including inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor-α, and interleukin-6 (IL-6) at both the mRNA and protein levels. Similarly, T. claveryi extract exhibited comparable inhibitory effects, except for the expression of IL-6 and COX-2 at the protein level, where no significant effect was observed. Moreover, both studied extracts significantly downregulated the microRNA expression levels of miR-21, miR-146a, and miR-155, suggesting that T. boudieri and T. claveryi suppress the inflammatory response in LPS/IFN-γ-stimulated RAW 264.7 cells through an epigenetic mechanism. Furthermore, our study reveals a new mechanism for the anti-inflammatory properties of desert truffle extracts. We show for the first time that Terfezia extracts do not rely on the nuclear factor erythroid 2-related factor 2 pathway, previously linked to anti-inflammatory responses. This expands our understanding of natural product anti-inflammatory mechanisms and could have important implications for developing new therapies. To account for differences in truffle effects, extracts prepared were subjected to secondary metabolites profiling using UPLC-MS. UPLC-MS led to the annotation of 87 secondary metabolites belonging to various classes, including amino acids, carbohydrates, alkaloids, amides, fatty acids, sterols, and phenolic compounds. Therefore, these results indicate that T. boudieri and T. claveryi exhibit anti-inflammatory activities through suppressing multiple inflammatory mediators and cytokines and may be potential anti-inflammatory agents.
Scalp acupuncture alleviates cerebral ischemic stroke-induced motor dysfunction in rats via regulating endoplasmic reticulum stress and ER-phagy
Authors: Zhang Yuxin , Lou Huijuan , Lu Jing , Tang Xiaolei , Pang Tingting , Lei Siyuan , Cong Deyu , Wang Yufeng , Sun Liwei
Published: June 2023

Cerebral ischemic stroke is a high-risk disease and imposes heavy burdens on patients in china. Acupuncture has been used for thousands of years to treat motor dysfunction, cognitive disorder and language barrier caused by cerebral ischemic stroke. Acupoint lines, vertex middle line and anterior oblique line of vertex temple, are always employed to treat cerebral ischemic stroke. However, the mechanism of the two acupoint lines in relieving cerebral ischemic stroke needs further exploration. In the present study, scalp acupuncture treatment alleviated the motor dysfunction, brain damage, and cell death induced by middle cerebral artery occlusion (MCAO) in rats. Proteomics analysis and ultrastructure observation indicated that endoplasmic reticulum and lysosomes might involve in the mechanism of the scalp acupuncture treatment in suppressing MCAO-triggered neural deficits. Effect of the scalp acupuncture treatment on ER stress was then investigated and found that the activation of ER stress mediators, including PERK, IRE1, and ATF6, was downregulated after the scalp acupuncture treatment. Co-localisation analysis of KDEL and CD63 showed that the engulfment of ER fragments by lysosomes was accelerated by the scalp acupuncture treatment. Moreover, expression of pro-apoptotic protein CHOP, phosphorylated-JNK, cleaved capases-3 and -9 also decreased after the scalp acupuncture. In conclusion, the present study showed that scalp acupuncture of vertex middle line and anterior oblique line of vertex temple may alleviate cerebral ischemic stroke by inhibiting ER stress-accelerated apoptosis.
Interoceptive abilities facilitate taking another’s spatial perspective
Authors: Baiano Chiara , Job Xavier , Kirsch Louise P. , Auvray Malika
Published: June 2023

Information can be perceived from a multiplicity of spatial perspectives, which is central to effectively understanding and interacting with our environment and other people. Interoception, the sense of the physiological state of our body, is also a fundamental component contributing to our perception. However, whether the perception of our inner body signals influences our ability to adopt and flexibly change between different spatial perspectives remains poorly understood. To investigate this, 90 participants completed tasks assessing multiple dimensions of interoception (interoceptive sensibility, cardiac interoceptive accuracy and awareness) and the Graphesthesia task to assess tactile spatial perspective-taking and its flexibility. The results revealed that higher cardiac interoceptive awareness is associated with greater consistency in adopting a perspective decentred from the self. Second, higher cardiac interoceptive accuracy was associated with slower and less accurate performance in switching from a decentred to an egocentred perspective. These results show that interoceptive abilities facilitate decentred spatial perspective-taking, likely reflecting stronger perceived boundaries between internal states and the external world.
Risk of developing chronic kidney disease in young-onset Type 2 diabetes in Korea
Authors: Lee Joonyub , Lee Seung-Hwan , Yoon Kun-Ho , Cho Jae Hyoung , Han Kyungdo , Yang Yeoree
Published: June 2023

We investigated the risk of developing chronic kidney disease (CKD) in patients with young-onset Type 2 diabetes (YOD, diagnosed age < 40 years). We enrolled 84,384 patients aged 20–64 who started anti-diabetic medication between 2010 and 2011 from the Korea National Health Insurance Sharing Service; patients with Type 1 diabetes or a history of CKD were excluded. Multivariate logistic regression analyses were performed to adjust for YOD-distinct variables and compare the incidence of CKD between YOD and late-onset diabetes (LOD, diagnosed age ≥ 40 years). During the median observation period of 5.16 years (interquartile range: 4.58–5.77 years), 1480 out of 77,039 LOD patients and 34 out of 7345 YOD patients developed CKD. Patients with YOD had distinct baseline characteristics compared with the patients with LOD. The odds ratio of developing CKD in patients with YOD over LOD was 1.70 (95% CI 1.15–2.51) after adjusting clinically distinct variables. The increased CKD odds in YOD compared with LOD was greater in the non-smoking group (OR 2.03, 95% CI 1.26–3.26) than in the smoking group (OR 1.49, 95% CI 0.74–2.98, p = 0.0393 for interaction). Among YOD patients, hypertension (34.76% vs. 64.71%, p = 0.0003), dyslipidemia (46.87% vs. 73.53%, p = 0.0019), and sulfonylurea use (35.54% vs. 52.94%, p = 0.0345) were associated with CKD development. YOD patients have a greater risk of developing CKD than LOD patients after adjusting clinically distinct variables.
FRET analysis of the temperature-induced structural changes in human TRPV3
Authors: Kim Jinyoung , Won Jongdae , Chung Dong Kyu , Lee Hyung Ho
Published: June 2023

Transient receptor potential vanilloid member 3 (TRPV3) is an ion channel that plays a critical role in temperature sensing in skin. There have been active studies on how TRPV3, which is also known as one of the temperature-sensitive transient receptor potential (thermoTRP) channels, responds to temperature. However, the previous studies were mostly based on TRPV3 originating from mice or rats. Here, we focus on human TRPV3 (hTRPV3) and show that which domain of hTRPV3 undergoes conformational changes as temperature increases by Förster resonance energy transfer (FRET) assay. During the heat-induced activation of hTRPV3, the linker domain close to C-terminus, that is, the C-terminal domain shows a largest structural change whereas there is little change in the ankyrin repeat domain (ARD). Interestingly, the activation of hTRPV3 by an agonist shows structural change patterns that are completely different from those observed during activation by heat; we observe structural changes in ARD and S2–S3 linker after ligand stimulation whereas relatively little change is observed when stimulated by heat. Our results provide insight into the thermal activation of hTRPV3 channel.
A causal link between mental imagery and affect-laden perception of climate change related risks
Authors: Karlsson Hulda , Asutay Erkin , Västfjäll Daniel
Published: June 2023

Previous studies have shed light on the importance of affect in risk perception and the role of mental imagery in generating affect. In the current study, we explore the causal relationship between mental imagery, affect, and risk perception by systematically varying the level of mental imagery in three levels (i.e., enhanced, spontaneous, or prevented). In light of the increasing environmental risk of adverse events caused by climate change, we operationalize risk as participants' perceived risk of climate change. One-thousand-fifty-five participants were recruited online and randomized to one of three levels of mental imagery. As predicted, we found a causal link between the level of mental imagery, affective experience, and perceived risk of climate change, in that enhanced mental imagery caused a larger decrease in positive affective valence and a larger increase in perceived risk of climate change. We argue that mental imagery enhances the negative affect associated with the risk event by creating a perceptual experience that mimics seeing the environmental risk events.
Changes in pre- and in-hospital management and outcomes among children with out-of-hospital cardiac arrest between 2012 and 2017 in Kanto, Japan
Authors: Ishihara Tadashi , Sasaki Ryuji , Enomoto Yuki , Amagasa Shunsuke , Yasuda Masato , Ohnishi Shima
Published: June 2023

Previously, the SOS-KANTO 2012 studies, conducted in the Kanto area of Japan, reported a summary of outcomes in patients with out-of-hospital cardiac arrest (OHCA). This sub-analysis of the SOS-KANTO study 2017 aimed to evaluate the neurological outcomes of paediatric OHCA patients, by comparing the SOS-KANTO 2012 and 2017 studies. All OHCA patients, aged < 18 years, who were transported to the participating hospitals by EMS personnel were included in both SOS-KANTO studies (2012 and 2017). The number of survival patients with favourable neurological outcomes (paediatric cerebral performance category 1 or 2) at 1 month did not improve between 2012 and 2017. There was no significant difference in achievement of pre-hospital return of spontaneous circulation (ROSC) [odds ratio (OR): 2.00, 95% confidence interval (95% CI): 0.50–7.99, p = 0.50] and favourable outcome at 1 month [OR: 0.67, 95% CI: 0.11–3.99, p = 1] between the two studies, matched by age, witnessed arrest, bystander CPR, aetiology of OHCA, and time from call to EMS arrival. Multivariable logistic regression showed no significant difference in the achievement of pre-hospital ROSC and favourable outcomes at 1 month between the two studies.
Thermal aerial culling for the control of vertebrate pest populations
Authors: Cox Tarnya E. , Paine David , O’Dwyer-Hall Emma , Matthews Robert , Blumson Tony , Florance Brenton , Fielder Kate , Tarran Myall , Korcz Matt , Wiebkin Annelise , Hamnett Peter W. , Bradshaw Corey J. A. , Page Brad
Published: June 2023

Helicopter-based shooting is an effective management tool for large vertebrate pest animals. However, animals in low-density populations and/or dense habitat can be difficult to locate visually. Thermal-imaging technology can increase detections in these conditions. We used thermal-imaging equipment with a specific helicopter crew configuration to assist in aerial culling for feral pigs (Sus scrofa) and fallow deer (Dama dama) in South Australia in 2021. Seventy-two percent of pigs and 53% of deer were first detected in dense canopy/tall forest habitat. Median time from the first impact shot to incapacitation was < 12 s. The culling rate (animals hour−1) doubled compared to visual shoots over the same populations and the wounding rate was zero resulting in a incapacitation efficiency of 100%. The crew configuration gave the shooter a wide field of view and the thermal operator behind the shooter provided essential support to find new and escaping animals, and to confirm species identification and successful removal. The crew configuration allowed for successful target acquisition and tracking, with reduced target escape. The approach can increase the efficiency of aerial culling, has the potential to increase the success of programs where eradication is a viable option, and can improve animal welfare outcomes by reducing wounding rates and the escape of target animals.
Transcriptome changes during osteogenesis of porcine mesenchymal stem cells derived from different types of synovial membranes and genetic background
Authors: Li Shuaichen , Siengdee Puntita , Oster Michael , Reyer Henry , Wimmers Klaus , Ponsuksili Siriluck
Published: June 2023

Synovial membrane mesenchymal stem cells (SMSCs) often serve as in vitro model for bone disease, but the molecular mechanisms driving osteogenesis in SMSCs from different donor cells of various sources and breeds remain unclear. In this study, porcine SMSCs isolated from adipose synovium (FP) and fibrous synovium (FS) of Angeln Saddleback (AS) and German Landrace (DL) were used to discover the signaling network change after osteogenic induction. During osteogenic differentiation, mineral deposition was first observed at day 14 and further increased until day 21. Transcriptional changes between day 1 and day 21 were enriched in several signaling pathways, including Wnt, PI3K-Akt, and TGF-beta pathway. Certain pathways related to osteogenesis, including osteoblast differentiation, regulation of bone mineralization, and BMP signaling pathway, were enriched at late time points, as confirmed by the osteogenic markers ALPL, COL1A1, and NANOG. A fraction of differentially expressed genes (DEGs) were found between FP and FS, while DEGs between AS and DL increased during the differentiation phase until day 7 and then decreased from day 14 to day 21. These genes are involved in several important signaling pathways, including TGF-beta, Wnt, and lipid-related signaling pathways, suggesting that SMSCs from these two breeds have different osteogenic capabilities.
Usefulness of two-dimensional shear wave elastography in the assessment of non-alcoholic fatty liver disease in children and adolescents
Authors: Yoon Jong Seo , Lim Kyoung Ja , Hwang Il Tae
Published: June 2023

Two-dimensional shear wave elastography (2D-SWE) evaluates liver stiffness using a non-invasive method, but studies in the paediatric population are rare. This study evaluated the role of 2D-SWE in the diagnosis and severity of paediatric non-alcoholic fatty liver disease (NAFLD). In total, 131 patients with NAFLD and 25 healthy controls were enrolled in this study. The diagnosis and severity of NAFLD were initially assessed using the ultrasound fatty liver index (US-FLI), and all participants underwent 2D-SWE. US-FLI semi-quantitatively measures the severity of NAFLD on a scale of 2–8. The assessment of liver stiffness measurement (LSM) by 2D-SWE is presented in kilopascals (kPa). The NAFLD group was characterised by significantly higher LSM (4.40 ± 0.90 kPa) than the control group (3.76 ± 0.28 kPa) (P < 0.001). 2D-SWE significantly correlated with age, height, weight, body mass index, glucose, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, US-FLI, and triglyceride-glucose index (P < 0.001). In the receiver operating characteristic curve analysis, the area under the curve of LSM for predicting US-FLI ≥ 2 and ≥ 6 was 0.784 (P < 0.001) and 0.819 (P < 0.001), respectively. In conclusion, we suggest that 2D-SWE can be used as a non-invasive diagnostic tool for diagnosing and assessing the severity of paediatric NAFLD.
Biomolecular condensates – extant relics or evolving microcompartments?
Authors: Rangachari Vijayaraghavan
Published: June 2023

Unprecedented discoveries during the past decade have unearthed the ubiquitous presence of biomolecular condensates (BCs) in diverse organisms and their involvement in a plethora of biological functions. A predominant number of BCs involve coacervation of RNA and proteins that demix from homogenous solutions by a process of phase separation well described by liquid-liquid phase separation (LLPS), which results in a phase with higher concentration and density from the bulk solution. BCs provide a simple and effective means to achieve reversible spatiotemporal control of cellular processes and adaptation to environmental stimuli in an energy-independent manner. The journey into the past of this phenomenon provides clues to the evolutionary origins of life itself. Here I assemble some current and historic discoveries on LLPS to contemplate whether BCs are extant biological hubs or evolving microcompartments. I conclude that BCs in biology could be extant as a phenomenon but are co-evolving as functionally and compositionally complex microcompartments in cells alongside the membrane-bound organelles.
Quantitative fat analysis of milk using a line-illumination spatially offset Raman probe through carton packaging
Authors: Song Si Won , Jeong Ye Chan , Park Chan Ryang , Kim Hyung Min
Published: June 2023

Milk is a popular dairy product that provides various nutrients, but consuming too much saturated fat from milk can increase the risk of diseases and obesity.
A liquid chromatography-miniature mass spectrometry (LC-Mini MS) method for quantitative analysis of risperidone and 9-hydroxyrisperidone in plasma
Authors: Gu Hao , Dai Guoxin , Teng Zhongqiu , Geng Lina , Xu Wei
Published: June 2023

A liquid chromatography-miniature mass spectrometry system with an optimized electrospray ionization interface setup was developed. It was used to determine risperidone and the active metabolite 9-hydroxyrisperidone in plasma.
Enabling a universal lateral flow readout for DNA strand displacement via disassembling chemical labels
Authors: Peng Wanting , Tan Yun , Shen Chenlan , Tang Yanan , Li Feng
Published: June 2023

A novel disassembling chemical label strategy is developed to enable universal lateral flow readout for DNA strand displacement reactions.
A mononuclear, terminal titanium(iii) imido
Authors: Mohar Jacob S. , Reinholdt Anders , Keller Taylor M. , Carroll Patrick J. , Telser Joshua , Mindiola Daniel J.
Published: June 2023

We report the first mononuclear TiIII complex possessing a terminal imido ligand.
Regulation of thrombin activity by ligand-induced topological alteration in a thrombin-binding aptamer
Authors: Sasaki Shogo , Ma Yue , Hirokawa Takatsugu , Ikebukuro Kazunori , Tera Masayuki , Nagasawa Kazuo
Published: June 2023

The function of the thrombin-binding aptamer was regulated by the G-quadruplex topology-altering ligand of L2H2-2M2EA-6LCO, thereby controlling thrombin activity.
Water coordinated Co-MOFs with 1D/2D network structure and highly enhanced electrocatalytic OER activity
Authors: Muthukumar Pandi , Arunkumar Gunasekaran , Pannipara Mehboobali , Al-Sehemi Abdullah G. , Moon Dohyun , Anthony Savarimuthu Philip
Published: June 2023

Water coordinated cobalt-metal organic frameworks (Co-MOFs) exhibited network structure dependent strong electrocatalytic OER activity in alkaline medium.
Structural insights into mechanical anisotropy in ambrisentan polymorphs
Authors: Haneef Jamshed , Markad Datta , Chadha Renu , Kumar Amit , Kumar Navin
Published: June 2023

Structural insights and nanoindentation experiments suggest that form II of ambrisentan demonstrated relatively higher plasticity and good tabletability as compared to commercial form I.
Formation of one-dimensional hierarchical MoO2@C–Ni/CoNi hybrids as highly efficient catalysts and protein adsorbents
Authors: Xie Songbo , Xiao Yang , Lu Na , Zhang Min
Published: June 2023

We have developed a facile approach to produce a hierarchical carbon tubular structure with Ni/NiCo NPs intercalated with MoO2 NPs, which manifested excellent performance in protein adsorption and the reduction of 4-nitrophenol.
Ammonium affects the wet chemical network of HCN: feedback between prebiotic chemistry and materials science
Authors: Pérez-Fernández Cristina , Vega Jorge , de la Fuente José L. , Mateo-Martí Eva , Valles Pilar , Ruiz-Bermejo Marta
Published: June 2023

The ammonium cation has a significant influence on the wet chemistry of HCN, modulating the properties of the obtained macromolecular systems.
The role of native point defects and donor impurities in the electrical properties of ZnSb2O4: a hybrid density-functional study
Authors: Charoenphon Supparat , Tubtimtae Auttasit , Watanabe Isao , Jungthawan Sirichok , T-Thienprasert Jiraroj , Boonchun Adisak , Reunchan Pakpoom
Published: June 2023

Gallium is the most viable donor dopant. However, the pinned Fermi level remains far from the conduction band edge, resulting in a semi-insulating material. It is not easy to dope n-type ZnSb2O4.
Mechanistic insights for regulating the site occupancy, valence states and optical transitions of Mn ions in yttrium–aluminum garnets via codoping
Authors: Chen Qiaoling , Liu Mingzhe , Ma Chong-Geng , Duan Chang-Kui
Published: June 2023

Codoping effects on the octahedral and dodecahedral coordinated site occupancies, and 2+, 3+, and 4+ valence states of Mn ions in solids are analyzed using first-principles calculations, and the optical transitions of Mn activators are rationalized.
Matrix-isolation vibrational circular dichroism (VCD) spectroscopy of chiral 1-phenyl-1-propanol
Authors: Grassin Corentin , Merten Christian
Published: June 2023

As the effect of self-aggregation of the title compound was not particularly strong in solution phase VCD spectra, we use matrix-isolation VCD spectroscopy to reveal the very subtle spectral features of dimers and higher aggregates.
Preparation of MOF-derived ZnO/Co3O4 nanocages and their sensing performance toward H2S
Authors: Liu Han , Kong Jiawei , Dong Zhe , Zhao Yongmei , An Baoli , Dong Junping , Xu Jiaqiang , Wang Xiaohong
Published: June 2023

ZnO/Co3O4 nanocages were synthesized by using MOFs as a sacrificial template. The ZnO/Co3O4 sensor enables the detection of H2S with an ultra-low detection limit (10 ppb) and superior sensitivity at 120 °C.
Effect of virgin coconut oil on body weight, white fat depots, and biochemical and morphological parameters in mice fed standard or high-fat diets
Authors: Silva Aline Almeida da , Pérez Elisangela Martins da Silva , Figueiredo Ingrid Samantha Tavares de , Alencar Nylane Maria Nunes de , Alves Ana Paula Negreiros Nunes , Fernandes Fabiano André Narciso , Vasconcelos Renata Prado , Oliveira Ariclécio Cunha de , Gaban Socorro Vanesca Frota
Published: June 2023

This study investigated the effects of virgin coconut oil (VCO) on body weight, white fat depots, and biochemical and morphological parameters in male Swiss mice fed standard (SD) or high-fat (HFD) diets.
Correction: Uncovering the effect of Moringa oleifera Lam. leaf addition to Fuzhuan Brick Tea on sensory properties, volatile profiles and anti-obesity activity
Authors: Li Xin , Shi Caihong , Wang Shuxuan , Wang Shuang , Wang Xin , Lü Xin
Published: June 2023

Correction for ‘Uncovering the effect of Moringa oleifera Lam. leaf addition to Fuzhuan Brick Tea on sensory properties, volatile profiles and anti-obesity activity’ by Xin Li et al., Food Funct., 2023, 14, 2404–2415, https://doi.org/10.1039/D2FO03531F.
High efficiency coupled electrocatalytic CO2 reduction to C2H4 with 5-hydroxymethylfurfural oxidation over Cu-based nanoflower electrocatalysts
Authors: Zhang Zonghang , Liu Shan , Wu Zhao , Chen Xiaoyan , Wang Jingui , Gao Yuji , Wang Shuai , Tao Furong , Lv Guangqiang
Published: June 2023

CO2 electroreduction and 5-hydroxymethylfurfural electrooxidation were coupled together over Cu base nanoflower catalyst and faradaic efficiency of FDCA and C2H4 reached to 96.6% and 74.5% respectively at a cell voltage of 2.75 V.
Design, synthesis, and evaluation of BTK-targeting PROTACs with optimized bioavailability in vitro and in vivo
Authors: Sun Yonghui , Yang Zimo , Zhang Zhimin , Li Zhen , Guo Liubin , Pan Hao , Luo Xin , Liu Dongzhou , Rao Yu
Published: June 2023

Development of a novel PROTAC molecule targeting BTK protein with better PK properties in vivo.
Exploitation of active site flexibility-low temperature activity relation for engineering broad range temperature active enzymes
Authors: Dasetty Siva , Zajac Jonathan W. P. , Sarupria Sapna
Published: June 2023

Can we modulate active site flexibility to engineer broad range temperature activity in thermophilic enzymes?
A dual stimuli-responsive smart soft carrier using multi-material 4D printing
Authors: Choi Inyoung , Jang Saeeun , Jung Seunggyeom , Woo Seohyun , Kim Jinyoung , Bak Cheol , Lee Yongmin , Park Sukho
Published: June 2023

A smart soft carrier fabricated by 4D printing using responsive hydrogels shows controllable open and close motion and movement to a desired position using NIR laser and magnetic field, which propose delivery of various cargoes and living organisms.
Hierarchically porous CexZr1−xO2 materials prepared by solvent volatilization for highly efficient synthesis of DMC from CO2 and methanol
Authors: Yang Guanling , Wang Haobo , Jia Aizhong , Li Jingde , Wang Yanji
Published: June 2023

The Zr-doping endowed the synthesized Ce0.9Zr0.1O2 material with excellent catalytic performance due to the increased number of oxygen vacancies and simultaneously improved its stability by enhancing the hydrophobicity of the synthesized material.