bluuebunny/crossref_metadata_2025 huggingface dataset:
The regulation of efferocytosis signaling pathways and adipose tissue homeostasis in physiological conditions and obesity: Current understanding and treatment options
Authors: Tajbakhsh Amir , Gheibihayat Seyed Mohammad , Karami Neda , Savardashtaki Amir , Butler Alexandra E. , Rizzo Manfredi , Sahebkar Amirhossein
Published: June 2022

Obesity is associated with changes in the resolution of acute inflammation that contribute to the clinical complications. The exact mechanisms underlying unresolved inflammation in obesity are not fully understood. Adipocyte death leads to pro‐inflammatory adipose tissue macrophages, stimulating additional adipocyte apoptosis. Thus, a complex and tightly regulated process to inhibit inflammation and maintain homeostasis after adipocyte apoptosis is needed to maintain health. In normal condition, a specialized phagocytic process (efferocytosis) performs this function, clearing necrotic and apoptotic cells (ACs) and controlling inflammation. For efficient and continued efferocytosis, phagocytes must internalize multiple ACs in physiological conditions and handle the excess metabolic burden in adipose tissue. In obesity, this control is lost and can be an important hallmark of the disease. In this regard, the deficiency of efferocytosis leads to delayed resolution of acute inflammation and can result in ongoing inflammation, immune system dysfunction, and insulin resistance in obesity. Hence, efficient clearance of ACs by M2 macrophages could limit long‐term inflammation and ensue clinical complications, such as cardiovascular disease and diabetes. This review elaborates upon the molecular mechanisms to identify efferocytosis regulators in obesity, and the mechanisms that can improve efferocytosis and reduce obesity‐related complications, such as the use of pharmacological agents and regular exercise.
Confocal microscopy in oral cancer and oral potentially malignant disorders: A systematic review
Authors: Ramani Rishi S. , Tan Ivy , Bussau Lindsay , Angel Christopher M. , McCullough Michael , Yap Tami
Published: June 2022

Objective

To systematically identify and summarise current research on the utility of confocal microscopy in oral squamous cell carcinoma and oral epithelial dysplasia in oral potentially malignant disorders.

Methods

Databases Medline, Embase, Evidence‐Based Medicine, and Web of Science were searched with articles screened and included if their primary objective was the use of a confocal microscope in diagnosis of oral cancer or epithelial dysplasia, in vivo or ex vivo.

Results and Discussion

Twenty‐eight relevant studies were identified of which 21 studies included oral squamous cell carcinoma specimens. Fifteen studies included in vivo use. The studies included both qualitative and fluorescence confocal microscope and reflectance confocal microscope analysis along with quantitative analysis of carcinoma and dysplasia. Thirteen studies reported the predictive value of their confocal device in the diagnosis of dysplasia and carcinoma. The quantitative software‐based studies show promise in objectifying the diagnostic process for identifying abnormalities within the microstructure of the oral mucosa.

Conclusions

There was heterogeneity in the criteria for diagnosis of dysplasia and oral squamous cell carcinoma with experience levels of assessors impacting method efficacy. Both qualitative and quantitative confocal assessment methodologies have been explored, the latter highlighting the potential of future machine‐augmented diagnostic precision.
The autotetraploid potato genome provides insights into highly heterozygous species
Authors: Wang Fang , Xia Zhiqiang , Zou Meiling , Zhao Long , Jiang Sirong , Zhou Yun , Zhang Chenji , Ma Yongzhen , Bao Yuting , Sun Haihong , Wang Wenquan , Wang Jian
Published: June 2022

Potato (Solanum tuberosum L.) originated in the Andes and evolved its vegetative propagation strategy through short day‐dependent tuber development. Herein, we present a high‐quality, chromosome‐scale reference genome sequence of a tetraploid potato cultivar. The total length of this genome assembly was 2.67 Gb, with scaffold N50 and contig N50 sizes of 46.24 and 2.19 Mb, respectively. In total, 1.69 Gb repetitive sequences were obtained through de novo annotation, and long terminal repeats were the main transposable elements. A total of 126 070 protein‐coding genes were annotated, of which 125 077 (99.21%) were located on chromosomes. The 48 chromosomes were classified into four haplotypes. We annotated 31 506 homologous genes, including 5913 (18.77%) genes with four homologues, 11 103 (35.24%) with three homologues, 12 177 (38.65%) with two homologues and 2313 (7.34%) with one homologue. MLH3, MSH6/7 and RFC3, which are the genes involved in the mismatch repair pathway, were found to be significantly expanded in the tetraploid potato genome relative to the diploid potato genome. Genome‐wide association analysis revealed that cytochrome P450, flavonoid synthesis, chalcone enzyme, glycosyl hydrolase and glycosyl transferase genes were significantly correlated with the flesh colours of potato tuber in 150 tetraploid potatoes. This study provides valuable insights into the highly heterozygous autotetraploid potato genome and may facilitate the development of tools for potato cultivar breeding and further studies on autotetraploid crops.
Pain avoidance and functional connectivity between insula and amygdala identifies suicidal attempters in patients with major depressive disorder using machine learning
Authors: Hao Ziyu , Li Huanhuan , Ouyang Lisheng , Sun Fang , Wen Xiaotong , Wang Xiang
Published: June 2022

Pain avoidance can effectively classify suicide attempters from non‐attempters among patients with major depressive disorder (MDD). However, the neural circuits underlying pain processing in suicide attempters have not been described comprehensively. In Study 1, we recruited MDD patients with a history of suicide attempts (MDD‐SA), and those without (MDD‐NSA) to examine the patterns of psychological pain using the latent profile analysis. Further, in Study 2, participants including the MDD‐SA, MDD‐NSA, and healthy controls underwent resting‐state functional magnetic resonance imaging. We used machine learning that included features of gray matter volume (GMV), the functional connectivity (FC) brain patterns of the region of interest, and behavioral data to identify suicide attempters. The results identified three latent classes of psychological pain in MDD patients: the low pain class (18.9%), the painful feeling class (37.2%), and the pain avoidance class (43.9%). Furthermore, the proportion of suicide attempters with high pain avoidance was the highest. The accuracy of multimodality classifiers (63%–92%) was significantly higher than that of brain‐only classifiers (56%–85%) and behavior‐only classifiers (64%–73%). Pain avoidance ranked first in the optimal feature set of the suicide attempt classification model. The crucial brain imaging features were FC between the left amygdala and right insula, right orbitofrontal and left thalamus, left anterior cingulate cortex and left insula, right orbitofrontal, amygdala, and the GMV of right thalamus. Additionally, the optimal feature set, including pain avoidance and crucial brain patterns of psychological pain neural circuits, was provided for the identification of suicide attempters.
The methyl‐CpG‐binding domain family member PEM1 is essential for Ubisch body formation and pollen exine development in rice
Authors: Song Yunyun , Tang Yongyan , Liu Lingtong , Xu Yunyuan , Wang Tai
Published: June 2022

Pollen exine is composed of finely‐organized nexine, bacula and tectum, and is crucial for pollen viability and function. Pollen exine development involves a complicated molecular network that coordinates the interaction between pollen and tapetal cells, as well as the biosynthesis, transport and assembly of sporopollenin precursors; however, our understanding of this network is very limited. Here, we report the roles of PEM1, a member of methyl‐CpG‐binding domain family, in rice pollen development. PEM1 expressed constitutively and, in anthers, its expression was detectable in tapetal cells and pollen. This predicted PEM1 protein of 240 kDa had multiple epigenetic‐related domains. pem1 mutants exhibited abnormal Ubisch bodies, delayed exine occurrence and, finally, defective exine, including invisible bacula, amorphous and thickened nexine and tectum layer structures, and also had the phenotype of increased anther cuticle. The mutation in PEM1 did not affect the timely degradation of tapetum. Lipidomics revealed much higher wax and cutin contents in mutant anthers than in wild‐type. Accordingly, this mutation up‐regulated the expression of a set of genes implicated in transcriptional repression, signaling and diverse metabolic pathways. These results indicate that PEM1 mediates Ubisch body formation and pollen exine development mainly by negatively modulating the expression of genes. Thus, the PEM1‐mediated molecular network represents a route for insights into mechanisms underlying pollen development. PEM1 may be a master regulator of pollen exine development.
Comparison of median sternotomy closure‐related complication rates using orthopedic wire or suture in dogs: A multi‐institutional observational treatment effect analysis
Authors: Pilot Mariette A. , Lutchman Aaron , Hennet Julie , Anderson Davina , Robinson William , Rossanese Matteo , Chrysopoulos Angelos , Demetriou Jackie , De la Puerta Benito , Mullins Ronan A. , Brissot Hervé , Jeffery Nicholas , Chanoit Guillaume
Published: June 2022

Objective

To determine and compare median sternotomy (MS) closure‐related complication rates using orthopedic wire or suture in dogs.

Study design

Multi‐institutional, retrospective observational study with treatment effect analysis.

Animals

331 client‐owned dogs, of which 68 were excluded.

Methods

Medical records of dogs with MS were examined across nine referral centers (2004–2020). Signalment, weight, clinical presentation, surgical details, complications, and outcomes were recorded. Follow‐up was performed using patient records and email/telephone contact. Descriptive statistics, treatment effect analysis and logistic regression were performed.

Results

Median sternotomy closure was performed with wire in 115 dogs and suture in 148. Thirty‐seven dogs experienced closure‐related complications (14.1%), 20 in the wire group and 17 in the suture group. Twenty‐three were listed as mild, four as moderate and 10 as severe. Treatment effect analysis showed a mean of 2.3% reduction in closure‐related complications associated with using suture versus wire (95% CI: −9.1% to +4.5%). In multivariable logistic regression, the only factor associated with increased risk of closure‐related complications was dog size (p = .01). This effect was not modified by the type of closure used (interaction term: OR = 0.99 [95% CI: 0.96/1.01]).

Conclusion

The incidence of closure‐related complication after MS was low compared to previous reports. The likelihood of developing a closure‐related complication was equivalent between sutures and wires, independent of dog size, despite a higher proportion of complications seen in larger dogs (≥20 kg).

Clinical significance

Use of either orthopedic wire or suture appear to be an appropriate closure method for sternotomy in dogs of any size.
Neogastropod (Mollusca, Gastropoda) phylogeny: A step forward with mitogenomes
Authors: Lemarcis Thomas , Fedosov Alexander E. , Kantor Yuri I. , Abdelkrim Jawad , Zaharias Paul , Puillandre Nicolas
Published: June 2022

The Neogastropoda (Mollusca, Gastropoda) encompass more than 15,000 described species of marine predators, including several model organisms in toxinology, embryology and physiology. However, their phylogenetic relationships remain mostly unresolved and their classification unstable. We took advantage of the many mitogenomes published in GenBank to produce a new molecular phylogeny of the neogastropods. We completed the taxon sampling by using an in‐house bioinformatic pipeline to retrieve mitochondrial genes from 13 transcriptomes, corresponding to five families not represented in GenBank, for a final dataset of 113 taxa. Because mitogenomic data are prone to reconstruction artefacts, eight different evolutionary models were applied to reconstruct phylogenetic trees with IQTREE, RAxML and MrBayes. If the over‐parametrization of some models produced trees with aberrant internal long branches, the global topology of the trees remained stable over models and softwares, and several relationships were revealed or found supported here for the first time. However, even if our dataset encompasses 60% of the valid families of neogastropods, some key taxa are missing and should be added in the future before proposing a revision of the classification of the neogastropods. Our study also demonstrates that even complex models struggle to satisfactorily handle the evolutionary history of mitogenomes, still leading to long‐branch attractions in phylogenetic trees. Other approaches, such as reduced‐genome strategies, must be envisaged to fully resolve the neogastropod phylogeny.
Residents' Socio-Economic Characteristics and Types of Gated Communities as Significant Determinants of Neighbourhood Safety in Ibadan, Nigeria
Authors: Makinde Olusola Oladapo
Published: June 2022

This study examined the residents’ socio-economic characteristics, types of gated communities, and the perception of safety in Ibadan, Nigeria. A questionnaire survey method and a direct observation schedule checklist were used to obtain the primary data. Thirty gated communities (GCs) indicating almost half of the 57 GCs were evaluated. Of 4922 units in the study areas, 493 samples, signifying 10% were appraised using a systematic sampling technique. Information was obtained from components of resident socio-economic characteristics and physical characteristics of neighbourhoods, which include: surveillance, territoriality, image and milieu, physical and design condition, experiences and social capital. The study used a Likert scale of 1 to 5 that started from very poor to excellent to measure elements of the Perception of Safety Index (PSI). The data obtained were evaluated using descriptive and inferential statistics. The result shows the levels and pattern of criminal activities in the study areas and identifies methods used by residents to curb the trend which comprises: enclosed neighbourhoods and gated communities. Others include vigilantes, community patrol, corporate guards or private security, putting in place closed circuit television (CCTV), jungle justice and mob action. This study showed that age, GC type, and the last time residents experienced an attack among others were related significantly to the perception of safety (p < 0.05). The analysis yielded p-values of 0.023, 0.005 and 0.001 respectively. The study resolved that the safety requirements of neighbourhoods varied, wide-ranging and comprehensive. The pathways for making improvements included: crime prevention through environmental design, social interaction, surveillance and improvement in the concepts of neighbourhood design, surveillance, territoriality, image and milieu.
The Influence of Construction Project Team Effectiveness in Higher Institutions’ Building Projects: A Case from Nigeria
Authors: Hassan Bala , Waziri Abdullahi Yusuf , Usman Hamza , Ibrahim Yakubu
Published: June 2022

Projects are required to meet the stakeholders’ requirements on the stipulated time, quality and budget. The achievement of such requirements is related to team effectiveness. However, there is poor project time and cost performance in Nigeria such that the constructions initiated mostly escalate beyond the cost and time budgeted. The construction project teams in Nigeria are shrouded with dysfunctions leading to undesirable project outcomes. This study aims to examine the influence of project team effectiveness on project performance of higher educational institutions’ construction in Nigeria. A quantitative survey design was employed where 150 questionnaires were administered to construction projects team members in four higher educational institutions in Bauchi state, Nigeria. The result indicated that the team effectiveness factors of communication, role and responsibility as well as team relationships have a substantial influence on project performance. However, goal and objectives, leadership, as well as trust and values factors, do not have significant influence. Overall, the result shows that the variation in the project performance can be explained substantially by changes in the construction project team effectiveness (Adj. R2 =.585). The implication of this finding is that project performance in Nigerian higher educational institutions can be significantly improved by strengthening communications, roles and responsibilities as well as relationships among team members. Thus, this research contributed to the existing body of knowledge on the linkage between team effectiveness and project performance in the Nigeria higher educational institutions' construction projects. The study, therefore, recommended the improvement of team effectiveness factors of the industry by all projects’ stakeholders and participants.
Parametric Study and Correlation of Racetrack Shaped Jets for Leading Edge Impingement
Authors: Kulkarni Ritwik V. , Wright Lesley M.
Published: June 2022

This paper provides a detailed experimental investigation of heat transfer and pressure loss for leading edge jet impingement using square-edged, racetrack jets. Experiments were carried out over various parameters: jet-to-jet spacings (s/d) of 2, 4, 8; jet-to-target surface spacings (z/d) of 2 and 4; jet plate thicknesses (l/d) of 1.33, 2.6, and 4; and Reynolds numbers from 10,000 to 100,000. The results show that pressure loss and heat transfer decrease with increasing s/d and z/d. There is an interesting observation for jet plate thickness at l/d = 2.6—a local minima for both heat transfer and pressure loss is measured with the racetrack shaped jets. Using the exhaustive experimental data, design correlations are developed to estimate the surface Nusselt number and discharge coefficients within the domain of geometric and flow parameters. The novel correlations account for the parametric effects and can accurately predict the Nusselt number and discharge coefficient with deviations of 19.8% and 15.9%, respectively. These provide a capability for the engine designers to predict the heat transfer and pressure loss for leading edge jet impingement.
Scanning anode field emission microscopy of a single Si emitter
Authors: Rughoobur Girish , Ilori Olusoji O. , Akinwande Akintunde I.
Published: June 2022

Emitter tip radius nonuniformity results in exponential variations in emission current and a relatively low array utilization. Here, we provide a method of mapping the current and field-factor from a single emitter over a small area using a scanning anode field emission microscope. A dull W probe is used as the anode, and an array of emitters is fabricated on silicon (Si) wafers. We use a relatively wide spaced (100 μm pitch) emitter array with each emitter having an integrated Si pillar. Current-voltage characteristics are used to extract the field-factor and to experimentally demonstrate the mapping of the currents and field-factor of a single emitter. From emission spot sizes, the emission half-angles are measured to be <14° at anode voltages 2.5 kV and a minimum resolvable feature of 2–3 μm at 1.8 kV. We also determine the field-factor dependence with the distance between the anode and the emitter, where limiting the current becomes essential to prevent early burn-out of the emitter that could reduce the current. We also simulated the maximum currents tolerated by the pillar to assess the thermal effects on the emitter. Finite element modeling confirms the experimental trend in the field-factor with the distance between the anode and the emitter tip, resulting in a value of approximately 105 cm−1 for an emitter tip radius of 5 nm and an emitter-anode distance of 50 μm.
Deep learning–based integration of genetics with registry data for stratification of schizophrenia and depression
Authors: Allesøe Rosa Lundbye , Nudel Ron , Thompson Wesley K. , Wang Yunpeng , Nordentoft Merete , Børglum Anders D. , Hougaard David M. , Werge Thomas , Rasmussen Simon , Benros Michael Eriksen
Published: June 2022

Currently, psychiatric diagnoses are, in contrast to most other medical fields, based on subjective symptoms and observable signs and call for new and improved diagnostics to provide the most optimal care. On the basis of a deep learning approach, we performed unsupervised patient stratification of 19,636 patients with depression [major depressive disorder (MDD)] and/or schizophrenia (SCZ) and 22,467 population controls from the iPSYCH2012 case cohort. We integrated data of disorder severity, history of mental disorders and disease comorbidities, genetics, and medical birth data. From this, we stratified the individuals in six and seven unique clusters for MDD and SCZ, respectively. When censoring data until diagnosis, we could predict MDD clusters with areas under the curve (AUCs) of 0.54 to 0.80 and SCZ clusters with AUCs of 0.71 to 0.86. Overall cases and controls could be predicted with an AUC of 0.81, illustrating the utility of data-driven subgrouping in psychiatry.
Performance of islets of Langerhans conformally coated via an emulsion cross-linking method in diabetic rodents and nonhuman primates
Authors: Stock Aaron A. , Gonzalez Grisell C. , Pete Sophia I. , De Toni Teresa , Berman Dora M. , Rabassa Alexander , Diaz Waldo , Geary James C. , Willman Melissa , Jackson Joy M. , DeHaseth Noa H. , Ziebarth Noel M. , Hogan Anthony R. , Ricordi Camillo , Kenyon Norma S. , Tomei Alice A.
Published: June 2022

Polyethylene glycol (PEG)–based conformal coating (CC) encapsulation of transplanted islets is a promising β cell replacement therapy for the treatment of type 1 diabetes without chronic immunosuppression because it minimizes capsule thickness, graft volume, and insulin secretion delay. However, we show here that our original CC method, the direct method, requiring exposure of islets to low pH levels and inclusion of viscosity enhancers during coating, severely affected the viability, scalability, and biocompatibility of CC islets in nonhuman primate preclinical models of type 1 diabetes. We therefore developed and validated in vitro and in vivo, in several small- and large-animal models of type 1 diabetes, an augmented CC method—emulsion method—that achieves hydrogel CCs around islets at physiological pH for improved cytocompatibility, with PEG hydrogels for increased biocompatibility and with fivefold increase in encapsulation throughput for enhanced scalability.
Profiling of mature-stage human breast milk cells identifies six unique lactocyte subpopulations
Authors: Gleeson John P. , Chaudhary Namit , Fein Katherine C. , Doerfler Rose , Hredzak-Showalter Patricia , Whitehead Kathryn A.
Published: June 2022

Breast milk is chock-full of nutrients, immunological factors, and cells that aid infant development. Maternal cells are the least studied breast milk component, and their unique properties are difficult to identify using traditional techniques. Here, we characterized the cells in mature-stage breast milk from healthy donors at the protein, gene, and transcriptome levels. Holistic analysis of flow cytometry, quantitative polymerase chain reaction, and single-cell RNA sequencing data identified the predominant cell population as epithelial with smaller populations of macrophages and T cells. Two percent of epithelial cells expressed four stem cell markers: SOX2, TRA-1-60, NANOG, and SSEA4. Furthermore, milk contained six distinct epithelial lactocyte subpopulations, including three previously unidentified subpopulations programmed toward mucosal defense and intestinal development. Pseudotime analysis delineated the differentiation pathways of epithelial progenitors. Together, these data define healthy human maternal breast milk cells and provide a basis for their application in maternal and infant medicine.
Identification of an integrase-independent pathway of retrotransposition
Authors: Li Feng , Lee Michael , Esnault Caroline , Wendover Katie , Guo Yabin , Atkins Paul , Zaratiegui Mikel , Levin Henry L.
Published: June 2022

Retroviruses and long terminal repeat retrotransposons rely on integrase (IN) to insert their complementary DNA (cDNA) into the genome of host cells. Nevertheless, in the absence of IN, retroelements can retain notable levels of insertion activity. We have characterized the IN-independent pathway of Tf1 and found that insertion sites had homology to the primers of reverse transcription, which form single-stranded DNAs at the termini of the cDNA. In the absence of IN activity, a similar bias was observed with HIV-1. Our studies showed that the Tf1 insertions result from single-strand annealing, a noncanonical form of homologous recombination mediated by Rad52. By expanding our analysis of insertions to include repeat sequences, we found most formed tandem elements by inserting at preexisting copies of a related transposable element. Unexpectedly, we found that wild-type Tf1 uses the IN-independent pathway as an alternative mode of insertion.
Dynamic instability of dendrite tips generates the highly branched morphologies of sensory neurons
Authors: Shree Sonal , Sutradhar Sabyasachi , Trottier Olivier , Tu Yuhai , Liang Xin , Howard Jonathon
Published: June 2022

The highly ramified arbors of neuronal dendrites provide the substrate for the high connectivity and computational power of the brain. Altered dendritic morphology is associated with neuronal diseases. Many molecules have been shown to play crucial roles in shaping and maintaining dendrite morphology. However, the underlying principles by which molecular interactions generate branched morphologies are not understood. To elucidate these principles, we visualized the growth of dendrites throughout larval development of
Drosophila
sensory neurons and found that the tips of dendrites undergo dynamic instability, transitioning rapidly and stochastically between growing, shrinking, and paused states. By incorporating these measured dynamics into an agent-based computational model, we showed that the complex and highly variable dendritic morphologies of these cells are a consequence of the stochastic dynamics of their dendrite tips. These principles may generalize to branching of other neuronal cell types, as well as to branching at the subcellular and tissue levels.
Biological chemotaxis-guided self-thermophoretic nanoplatform augments colorectal cancer therapy through autonomous mucus penetration
Authors: Wang Zhi-Hao , Chu Mengyu , Yin Na , Huang Wanting , Liu Wei , Zhang Zhenzhong , Liu Junjie , Shi Jinjin
Published: June 2022

Oral drug delivery systems have great potential to treat colorectal cancer (CRC). However, the drug delivery efficiency is restricted by limited CRC-related intestine positioning and dense mucus barrier. Here, we present a biological chemotaxis-guided self-thermophoretic nanoplatform that facilitates precise intestinal positioning and autonomous mucus penetration. The nanoplatform introduces asymmetric platinum-sprayed mesoporous silica to achieve autonomous movement in intestinal mucus. Furthermore, inspired by the intense interaction between pathogenic microbes and CRC, the nanoplatform is camouflaged by
Staphylococcus aureus
membrane to precisely anchor in CRC-related intestine. Owing to 4.3-fold higher biological chemotactic anchoring of CRC-related intestine and 14.6-fold higher autonomous mucus penetration performance, the nanoplatform vastly improves the oral bioavailability of cisplatin, leading to a tumor inhibition rate of 99.1% on orthotopic CRC–bearing mice. Together, the exquisitely designed nanoplatform to overcome multiple physiological barriers provides a new horizon for the development of oral drug delivery systems.
Superdurable and fire-retardant structural coloration of carbon nanotubes
Authors: Chen Fengxiang , Huang Ya , Li Run , Zhang Shiliang , Jiang Qinyuan , Luo Yuxin , Wang Baoshun , Zhang Wenshuo , Wu Xueke , Wang Fei , Lyu Pei , Zhao Siming , Xu Weilin , Wei Fei , Zhang Rufan
Published: June 2022

Carbon nanotubes (CNTs) are promising candidates for numerous cutting-edge fields because of their excellent properties. However, the inherent black color of CNTs cannot satisfy the aesthetic/fashion requirement, and the flammability of CNTs severely restricts their application in high-temperature environments with oxygen. Here, we realized a structural coloration of CNTs by coating them with amorphous TiO
2
layers. By tuning the TiO
2
coating thickness, both CNT fibers and membranes exhibited controllable and brilliant colors, which exhibited remarkable superdurability that could endure 2000 cycles of laundering tests and more than 10 months of high-intensity ultraviolet irradiation. The TiO
2
-coated CNTs exhibited a notable fire-retardant performance and could endure 8 hours of fire burning. The structural coloration of CNTs with excellent fire retardance substantially improves their performance and broadens their applications.
CPK28-NLP7 module integrates cold-induced Ca
2+
signal and transcriptional reprogramming in
Arabidopsis
Authors: Ding Yanglin , Yang Hao , Wu Shifeng , Fu Diyi , Li Minze , Gong Zhizhong , Yang Shuhua
Published: June 2022

Exposure to cold triggers a spike in cytosolic calcium (Ca
2+
) that often leads to transcriptional reprogramming in plants. However, how this Ca
2+
signal is perceived and relayed to the downstream cold signaling pathway remains unknown. Here, we show that the CALCIUM-DEPENDENT PROTEIN KINASE 28 (CPK28) initiates a phosphorylation cascade to specify transcriptional reprogramming downstream of cold-induced Ca
2+
signal. Plasma membrane (PM)–localized CPK28 is activated rapidly upon cold shock within 10 seconds in a Ca
2+
-dependent manner. CPK28 then phosphorylates and promotes the nuclear translocation of NIN-LIKE PROTEIN 7 (NLP7), a transcription factor that specifies the transcriptional reprogramming of
cold-responsive
gene sets in response to Ca
2+
, thereby positively regulating plant response to cold stress. This study elucidates a previously unidentified mechanism by which the CPK28-NLP7 regulatory module integrates cold-evoked Ca
2+
signal and transcriptome and thus uncovers a key strategy for the rapid perception and transduction of cold signals from the PM to the nucleus.
Resilience of infaunal ecosystems during the Early Triassic greenhouse Earth
Authors: Feng Xueqian , Chen Zhong-Qiang , Benton Michael J. , Su Chunmei , Bottjer David J. , Cribb Alison T. , Li Ziheng , Zhao Laishi , Zhu Guangyou , Huang Yuangeng , Guo Zhen
Published: June 2022

The Permian-Triassic mass extinction severely depleted biodiversity, primarily observed in the body fossil of well-skeletonized animals. Understanding how whole ecosystems were affected and rebuilt following the crisis requires evidence from both skeletonized and soft-bodied animals; the best comprehensive information on soft-bodied animals comes from ichnofossils. We analyzed abundant trace fossils from 26 sections across the Permian-Triassic boundary in China and report key metrics of ichnodiversity, ichnodisparity, ecospace utilization, and ecosystem engineering. We find that infaunal ecologic structure was well established in the early Smithian. Decoupling of diversity between deposit feeders and suspension feeders in carbonate ramp-platform settings implies that an effect of trophic group amensalism could have delayed the recovery of nonmotile, suspension-feeding epifauna in the Early Triassic. This differential reaction of infaunal ecosystems to variable environmental controls thus played a substantial but heretofore little appreciated evolutionary and ecologic role in the overall recovery in the hot Early Triassic ocean.
Efficient delivery of a DNA aptamer-based biosensor into plant cells for glucose sensing through thiol-mediated uptake
Authors: Mou Quanbing , Xue Xueyi , Ma Yuan , Banik Mandira , Garcia Valeria , Guo Weijie , Wang Jiang , Song Tingjie , Chen Li-Qing , Lu Yi
Published: June 2022

DNA aptamers have been widely used as biosensors for detecting a variety of targets. Despite decades of success, they have not been applied to monitor any targets in plants, even though plants are a major platform for providing oxygen, food, and sustainable products ranging from energy fuels to chemicals, and high-value products such as pharmaceuticals. A major barrier to progress is a lack of efficient methods to deliver DNA into plant cells. We herein report a thiol-mediated uptake method that more efficiently delivers DNA into
Arabidopsis
and tobacco leaf cells than another state-of-the-art method, DNA nanostructures. Such a method allowed efficient delivery of a glucose DNA aptamer sensor into
Arabidopsis
for sensing glucose. This demonstration opens a new avenue to apply DNA aptamer sensors for functional studies of various targets, including metabolites, plant hormones, metal ions, and proteins in plants for a better understanding of the biodistribution and regulation of these species and their functions.
Neuromorphic computing hardware and neural architectures for robotics
Authors: Sandamirskaya Yulia , Kaboli Mohsen , Conradt Jorg , Celikel Tansu
Published: June 2022

Neuromorphic hardware enables fast and power-efficient neural network–based artificial intelligence that is well suited to solving robotic tasks. Neuromorphic algorithms can be further developed following neural computing principles and neural network architectures inspired by biological neural systems. In this Viewpoint, we provide an overview of recent insights from neuroscience that could enhance signal processing in artificial neural networks on chip and unlock innovative applications in robotics and autonomous intelligent systems. These insights uncover computing principles, primitives, and algorithms on different levels of abstraction and call for more research into the basis of neural computation and neuronally inspired computing hardware.
Interactions of Bacterial Toxin CNF1 and Host JAK1/2 Driven by Liquid-Liquid Phase Separation Enhance Macrophage Polarization
Authors: Sun Xuan , Yang Jianming , Deng Xueqin , Wei Yuting , Wang Changying , Guo Yaxiu , Yang Huan , Yang Liu , Miao Chunhui , Lv Junqiang , Xiao Yawen , Zhang Hong , Yao Zhi , Wang Quan
Published: June 2022

CNF1 is a key toxin secreted by UPEC, which induces inflammation during UPEC infections. CNF1 is well known to activate Rho GTPases to disturb host cell signaling pathways.
Cell Death in Escherichia coli: Incomplete Base Excision Repair under Depletion of DapB and Dxr Proteins
Authors: Azizoglu Reha Onur
Published: June 2022

The generation of reactive oxygen species (ROS) within the cell is a significantly shared aspect of bacterial cell death against different stress conditions. The main cell death mechanism due to the generation of reactive oxygen species is then the incomplete base excision repair (BER) in response to oxidized nucleotides.
Meta-Analysis of Altered Gut Microbiota Reveals Microbial and Metabolic Biomarkers for Colorectal Cancer
Authors: Avuthu Nagavardhini , Guda Chittibabu
Published: June 2022

Several studies showed associations between gut dysbiosis and CRC. Yet, the results are not conclusive due to cohort-specific associations that are influenced by genomic, dietary, and environmental stimuli and associated reproducibility issues with various analysis approaches.
Comparison and Correlation Analysis of Immune Function and Gut Microbiota of Broiler Chickens Raised in Double-Layer Cages and Litter Floor Pens
Authors: Song Bochen , Yan Shaojia , Li Peng , Li Guang , Gao Mingkun , Yan Lei , Lv Zengpeng , Guo Yuming
Published: June 2022

In China, the three-dimensional rearing system (cage) for broilers has gradually become a trend. In production, it was found that the incidence of disease in broiler chickens raised in cage systems was significantly higher than that of ground litter.
CRISPR-Cas9 Toolkit for Genome Editing in an Autotrophic CO
2
-Fixing Methanogenic Archaeon
Authors: Li Jie , Zhang Liuyang , Xu Qing , Zhang Wenting , Li Zhihua , Chen Lei , Dong Xiuzhu
Published: June 2022

Archaea are prokaryotes with intriguing biological characteristics. They possess bacterial cell structures but eukaryotic homologous information processing machinery and eukaryotic featured proteins.
Prognostic Significance of the Relative Load of KPC-Producing Klebsiella pneumoniae within the Intestinal Microbiota in a Prospective Cohort of Colonized Patients
Authors: Pérez-Nadales Elena , M. Natera Alejandra , Recio-Rufián Manuel , Guzmán-Puche Julia , Marín-Sanz Juan Antonio , Martín-Pérez Carlos , Cano Ángela , Castón Juan José , Elías-López Cristina , Machuca Isabel , Gutiérrez-Gutiérrez Belén , Martínez-Martínez Luis , Torre-Cisneros Julián
Published: June 2022

The rapid dissemination of carbapenemase-producing Enterobacterales represents a global public health threat. Increased relative load of KPC-producing
Klebsiella pneumoniae
(KPC-KP) within the intestinal microbiota has been associated with an increased risk of bloodstream infection by KPC-KP.
Halogen ratios in crustal fluids through time—Proxies for the emergence of aerobic life?
Authors: Fusswinkel Tobias , Niinikoski-Fusswinkel Paula , Wagner Thomas
Published: June 2022

Halogens (Cl, Br, I) are exceptional provenance tracers in crustal fluids because their ratios are not strongly altered during most fluid-rock interaction processes. The halogen systematics of metamorphic fluids are of particular interest because such fluids are key drivers of crustal-scale element fluxes and ore formation in orogenic belts, but they remain poorly studied due to analytical challenges. We present novel triple-halogen laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) fluid-inclusion data from metamorphic systems ranging in age from Archean to Phanerozoic. Our results show that the halogen signatures in Phanerozoic metamorphic fluids are controlled by variable degrees of organic-matter interaction in their source rocks, leading to increased I/Cl and decreased Br/I ratios relative to seawater. By contrast, Archean metamorphic fluids from organic matter–rich source rocks have low I/Cl and very high Br/I ratios, distinctly different from any known fluid source signature. We propose that these signatures nevertheless are consistent with organic-matter interaction because dominantly prokaryotic Archean lifeforms did not yet produce iodine-bearing metabolites. This prevented biosequestration and accumulation of iodine-rich organic matter in sediments and imposed halogen signatures onto Archean metamorphic fluids entirely unlike those in younger fluids.
Afghan Agenda in Current Canadian Politics
Authors: Issraelyan E. V.
Published: June 2022

Canada’s operation in Afghanistan has been unfolding during a critically important domestic political event, i.e., the federal elections of 2021. The election campaign had pooled the main attention and resources of the Canadian leadership, limiting its ability to act in Afghanistan. Despite the difficulties, the Liberal Government of Justin Trudeau has achieved a lot. Firstly, they have organized the evacuation of Canadians and of Afghans who worked with the Canadian Armed Forces during the US and NATO military mission. Secondly, Ottawa has defined its attitude towards the Taliban regime by refusing diplomatic recognition. Thirdly, the admission of Afghan refugees to Canada has begun. In each of these areas, the Liberal Government has successes and failures, which have caused acute controversy in the country.
Peasant Studies As a New Direction in Modern Studies of Russian Agrarian History
Authors: Babashkin V.
Published: June 2022

This article describes the circumstances under which a permanent interdisciplinary international seminar “Modern Concepts of Agrarian Development” arose in 1992. The roles of the Russian historian V.P. Danilov at the Institute of Russian History, Russian Academy of Sciences (IRH RAS) and the English historian-sociologist T. Shanin (Manchester University, Britain), as well as the role of the problems discussed at the meetings at the seminar and the publication of the seminar’s materials by the journal Otechestvennayaistoriya (Russian History) in the development of a new direction in Russian agrarian historical research, in the creation of this forum are shown. Suggestions are made about why the methodological approaches that gained popularity in the 1960s in Western Peasant Studies are difficult to apply to Russian-language historical publications on agrarian issues. An idea is given of some works of modern domestic historians that can rightfully be attributed to the direction of research called peasant studies.
Market Transformations in the 1990s in the Russian Village
Authors: Verbitskaya Olga
Published: June 2022

This article examines the agrarian reform of the 1990s in Russia. It is noted that its first version was developed by domestic agricultural scientists and was designed for the phased implementation of transformations for a period of at least 10 years. However, later, under pressure from Western experts, this project underwent significant adjustments, in accordance with which the market reform in the agrarian sector was carried out more radically and at a faster pace. It is shown that the main methods of market transformations in the countryside were price liberalization, denationalization and privatization of land, distribution of land shares to farmers, creation of a farmer’s way of life, disaggregation of former collective agricultural enterprises, their transfer to market forms of work, etc. The author believes that basically these transformations in the countryside were carried out formally and did not achieve their true goal. The reformers' hopes for the economic success of farms also turned out to be untenable, since their real number was extremely small, and their actual role in agricultural production was scanty. More than half of all products of the agricultural sector were produced by subsidiary farms, which were significantly replenished by the peasants who lost their jobs. At the end of the article, it was concluded that the agrarian reform, conceived with the aim of significantly increasing the efficiency of agriculture, did not justify the hopes: the tasks set were not fulfilled, and it only actually ruined agriculture. Over the 10 years of market transformations, the area under crops has significantly decreased, the number of livestock has decreased, production has fallen by more than 50%, and the level of labor mechanization has decreased by about 33%. As a result of the market transformations in the 1990s, the agricultural industry of Russia in terms of its main indicators was thrown back 30–40 years.
Participation of the Organs of the OGPU-NKVD of the Soviet Union in the Collectivization of Agriculture
Authors: Mozokhin O. B.
Published: June 2022

This article analyzes the role of the OGPU-NKVD in carrying out the policy of the All-Union Communist Party of Bolsheviks on the collectivization of agriculture, and it reports on the protest movements of the peasantry, on individual and collective protests against collectivization, and the suppression of these movements by punitive bodies. The measures of the authorities for the “liquidation of the kulaks as a class” and the organs of the OGPU-NKVD as a mechanism for carrying out repressions are specially studied.
Incidence and outcomes of pulmonary hypertension in the Ireland
Authors: Cullivan Sarah , Lennon Denise , Meghani Salima , Minnock Caitriona , McCullagh Brian , Gaine Sean
Published: June 2022

Introduction

Pulmonary hypertension (PH) is a progressive disease of the pulmonary vasculature, which is characterised by premature morbidity and mortality. The aim of this study is to define the characteristics of PH in the national PH unit (NPHU) in Ireland between 2010 and 2020.

Methods

Cases of PH which were referred to the NPHU between 2010 and 2020 were included. PH was defined as a mean pulmonary artery pressure ≥25 mm Hg at right heart catheterisation.

Results

Four hundred and fifteen cases of PH were identified during the study period. Group 1 pulmonary arterial hypertension (PAH) accounted for 39% (n=163) of cases, with a calculated annual incidence of 3.11 per million population (95% CI 1.53 to 4.70). The leading PAH subgroup was connective tissue disease-associated PAH (CTD-PAH), which was responsible for 49% of PAH referrals. This was followed by idiopathic PAH, with an estimated annual incidence of 0.63 cases per million population. The mean age at PAH diagnosis was 56±15 years and 86% (n=111) received double-combination or triple-combination therapy within the first 12 months of diagnosis. The 1-year, 3-year and 5-year transplant-free survival for PAH was 89%, 75% and 65%. This was significantly lower for individuals with CTD-PAH relative to other PAH subgroups (p<0.05).

Discussion

This study describes the incidence and outcomes of PH in Ireland. While the outcomes are comparable to other centres, the incidence of PAH and specific subgroups appears low, suggesting that improved disease awareness and case recognition are required. Furthermore, the survival of individuals with CTD-PAH is poor and requires additional exploration.
NY-ESO-1-specific redirected T cells with endogenous TCR knockdown mediate tumor response and cytokine release syndrome
Authors: Ishihara Mikiya , Kitano Shigehisa , Kageyama Shinichi , Miyahara Yoshihiro , Yamamoto Noboru , Kato Hidefumi , Mishima Hideyuki , Hattori Hiroyoshi , Funakoshi Takeru , Kojima Takashi , Sasada Tetsuro , Sato Eiichi , Okamoto Sachiko , Tomura Daisuke , Nukaya Ikuei , Chono Hideto , Mineno Junichi , Kairi Muhammad Faris , Diem Hoang Nguyen Phuong , Simoni Yannick , Nardin Alessandra , Newell Evan , Fehlings Michael , Ikeda Hiroaki , Watanabe Takashi , Shiku Hiroshi
Published: June 2022

Background

Because of the shortage of ideal cell surface antigens, the development of T-cell receptor (TCR)-engineered T cells (TCR-T) that target intracellular antigens such as NY-ESO-1 is a promising approach for treating patients with solid tumors. However, endogenous TCRs in vector-transduced T cells have been suggested to impair cell-surface expression of transduced TCR while generating mispaired TCRs that can become self-reactive.

Methods

We conducted a first-in-human phase I clinical trial with the TCR-transduced T-cell product (TBI-1301) in patients with NY-ESO-1-expressing solid tumors. In manufacturing TCR-T cells, we used a novel affinity-enhanced NY-ESO-1-specific TCR that was transduced by a retroviral vector that enables siRNA (small interfering RNA)-mediated silencing of endogenous TCR. The patients were divided into two cohorts. Cohort 1 was given a dose of 5×108cells (whole cells including TCR-T cells) preconditioned with 1500 mg/m2cyclophosphamide. Cohort 2 was given 5× 109cells preconditioned with 1500 mg/m2cyclophosphamide.

Results

In vitro study showed that both the CD8+and CD4+T fractions of TCR-T cells exhibited cytotoxic effects against NY-ESO-1-expressing tumor cells. Three patients and six patients were allocated to cohort 1 and cohort 2, respectively. Three of the six patients who received 5×109cells showed tumor response, while three patients developed early-onset cytokine release syndrome (CRS). One of the patients developed a grade 3 lung injury associated with the infiltration of the TCR-T cells. No siRNA-related adverse events other than CRS were observed. Cytokines including interleukin 6 I and monocyte chemotactic protein-1/chemokine (C-C motif) ligand (CCL2)

increased in the sera of patients with CRS. In vitro analysis showed these cytokines were not secreted from the T cells infused. A significant fraction of the manufactured T cells in patients with CRS was found to express either CD244, CD39, or both at high levels.

Conclusions

The trial showed that endogenous TCR-silenced and affinity-enhanced NY-ESO-1 TCR-T cells were safely administered except for grade 3 lung injury. The TCR-T cell infusion exhibited significant tumor response and early-onset CRS in patients with tumors that express NY-ESO-1 at high levels. The differentiation properties of the manufactured T cells may be prognostic for TCR-T-related CRS.

Trial registration number

NCT02366546.