bluuebunny/crossref_metadata_2025 huggingface dataset:
A spatiotemporal transcriptomic network dynamically modulates stalk development in maize
Authors: Le Liang , Guo Weijun , Du Danyao , Zhang Xiaoyuan , Wang Weixuan , Yu Jia , Wang Huan , Qiao Hong , Zhang Chunyi , Pu Li
Published: August 2022

Maize (Zea mays) is an important cereal crop with suitable stalk formation which is beneficial for acquiring an ideal agronomic trait to resist lodging and higher planting density. The elongation pattern of stalks arises from the variable growth of individual internodes driven by cell division and cell expansion comprising the maize stalk. However, the spatiotemporal dynamics and regulatory network of the maize stalk development and differentiation process remain unclear. Here, we report spatiotemporally resolved transcriptomes using all internodes of the whole stalks from developing maize at the elongation and maturation stages. We identified four distinct groups corresponding to four developmental zones and nine specific clusters with diverse spatiotemporal expression patterns among individual internodes of the stalk. Through weighted gene coexpression network analysis, we constructed transcriptional regulatory networks at a fine spatiotemporal resolution and uncovered key modules and candidate genes involved in internode maintenance, elongation, and division that determine stalk length and thickness in maize. Further CRISPR/Cas9‐mediated knockout validated the function of a cytochrome P450 gene, ZmD1, in the regulation of stalk length and thickness as predicted by the WGCN. Collectively, these results provide insights into the high genetic complexity of stalk development and the potentially valuable resources with ideal stalk lengths and widths for genetic improvements in maize.
Multiplexed promoter and gene editing in wheat using a virus‐based guide RNA delivery system
Authors: Wang Wei , Yu Zitong , He Fei , Bai Guihua , Trick Harold N. , Akhunova Alina , Akhunov Eduard
Published: August 2022

The low efficiency of genetic transformation and gene editing across diverse cultivars hinder the broad application of CRISPR technology for crop improvement. The development of virus‐based methods of CRISPR‐Cas system delivery into the plant cells holds great promise to overcome these limitations. Here, we perform direct inoculation of wheat leaves with the barley stripe mosaic virus (BSMV) transcripts to deliver guide RNAs (sgRNA) into the Cas9‐expressing wheat. We demonstrate that wheat inoculation with the pool of BSMV‐sgRNAs could be used to generate heritable precise deletions in the promoter region of a transcription factor and to perform multiplexed editing of agronomic genes. We transfer the high‐expressing locus of Cas9 into adapted spring and winter cultivars by marker‐assisted introgression and use of the BSMV‐sgRNAs to edit two agronomic genes. A strategy presented in our study could be applied to any adapted cultivar for creating new cis‐regulatory diversity or large‐scale editing of multiple genes in biological pathways or QTL regions, opening possibilities for the effective engineering of crop genomes, and accelerating gene discovery and trait improvement efforts.
Peptide Cysteine Thiols Act as Photostabilizer of Avobenzone through Stabilizing the Transition State of Keto‐Enol Tautomerization
Authors: Moi Smriti , Shekh Shamasoddin , Reddy K. Kasi Amarnath , Dhurjad Pooja , Sonti Rajesh , Gowd Konkallu Hanumae
Published: August 2022

Photostabilizers have been used to impart stability to an FDA‐approved chemical UV‐A filter avobenzone against the UV‐A radiations and sunlight. The thiol group of glutathione plays a critical role in imparting the photostabilization activity of glutathione on avobenzone. The current report aims to evaluate the photostabilization activity of multiple thiols containing cysteine peptides on avobenzone. Cysteine‐tripeptide and cysteine‐pentapeptide were chemically synthesized and characterized using mass spectrometry. Synthetic peptides were assessed for their photostabilization activity on the enolic‐form of the avobenzone under natural sunlight using UV spectroscopy in both protic and aprotic solvents. Unlike glutathione, which has pronounced activity in protic solvents, cysteine‐pentapeptide exhibits similar photoprotection activity in both protic and aprotic solvents. Computational calculations using DFT suggest that peptide cysteine thiols may assist in the reversal of the photoketonization process of avobenzone thereby exhibiting the photoprotection activity to the enolic‐form of avobenzone. Peptide cysteine thiols lower the activation energy barrier of keto‐to‐enol tautomerization of avobenzone by 30 kcal mol−1 by assisting the proton shuttle through a six‐membered transition state. The current report emphasizes the applications of peptide thiols in cosmetics and may help in the development of peptides as aesthetic medicines.
The gene LpBCP increased NaHCO3 resistance by enhancing lignin or ROS scavenging in the Nicotiana benthamiana
Authors: Jin S. , Wang X. , Dong Y. , Li G. , Chang X. , Zhang L. , Jin S.
Published: August 2022

Lilium pumilum is an excellent wildflower germplasm resource with high resistance to salinity stress. The gene LpBCP plays an important role in salinity tolerance of L. pumilum. Studying the molecular mechanism of salinity resistance in L. pumilum will provide insights into multiple aspects, including breeding better varieties, environmental protection, improving soil conditions, etc.

Conventional methods were used to determine different physiological indicators of Nicotiana benthamiana after NaHCO3 treatment, i.e. chlorophyll content, soluble phenol content and lignin content. RT‐qPCR was carried out to find expression of LpBCP in different organs and under abiotic stresses. DAB was used to detect H2O2 in leaves in situ. A yeast two‐hybrid system was used to screen for LpBCP interacting proteins.

LpBCP was cloned from bulbs of L. pumilum. The highest expression of LpBCP was in roots and bulbs of transgenic plants. LpBCP‐overexpressed plants showed less wilting, compared to WT plants. LpBCP transgenic plants have higher chlorophyll, soluble phenol and lignin content, and lower relative conductivity under 500 mM NaHCO3 stress. In addition, H2O2 scavenging in transgenic plants was much improved, indicating increased resistance to NaHCO3 stress. Thirteen LpBCP‐interacting proteins were screened using the yeast two‐hybrid method and five were associated with salt stress.

Based on our findings, LPBCP could be a key gene that can be used to improve L. pumilum salt tolerance.
Differentially reset transcriptomes and genome bias response orchestrate wheat response to phosphate deficiency
Authors: Wang Ruonan , Chen Yinglong , Kaur Gazaldeep , Wu Xiaoba , Nguyen Henry T. , Shen Renfang , Pandey Ajay Kumar , Lan Ping
Published: August 2022

Phosphorus (P) is an essential macronutrient for all organisms. Phosphate (Pi) deficiency reduces grain yield and quality in wheat. Understanding how wheat responds to Pi deficiency at the global transcriptional level remains limited. We revisited the available RNA‐seq transcriptome from Pi‐starved wheat roots and shoots subjected to Pi starvation. Genome‐wide transcriptome resetting was observed under Pi starvation, with a total of 917 and 2338 genes being differentially expressed in roots and shoots, respectively. Chromosomal distribution analysis of the gene triplets and differentially expressed genes (DEGs) revealed that the D genome displayed genome induction bias and, specifically, the chromosome 2D might be a key contributor to Pi‐limiting triggered gene expression response. Alterations in multiple metabolic pathways pertaining to secondary metabolites, transcription factors and Pi uptake‐related genes were evidenced. This study provides genomic insight and the dynamic landscape of the transcriptional changes contributing to the hexaploid wheat during Pi starvation. The outcomes of this study and the follow‐up experiments have the potential to assist the development of Pi‐efficient wheat cultivars.
Temporal dynamics of conflict adaptation across different conflict strengths
Authors: Zhang Mengke , Li Qing , Li Yilu , Chen Yongqiang , Gu Yan , Yin Shouhang , Chen Antao
Published: August 2022

Conflict adaptation is considered to reflect the adjustment of cognitive control, and it is critical for adaptive behavior. Despite intensive investigations on conflict adaptation, straightforward evidence on how changes in conflict strength influence the behavioral and neural dynamics of conflict adaptation remains scarce. To address this issue, we manipulated conflict strength by varying distractor–target congruency to investigate whether conflict strength per se or the expectancy of conflict strength triggers the adjustment of cognitive control. Behavioral and electroencephalographic (EEG) measures were recorded while participants performed a variant four‐choice flanker task without feature repetitions. The behavioral results showed that reaction times increased with increasing conflict strength. Importantly, there were conflict adaptations between the congruent and incongruent‐low, congruent and incongruent‐high, and incongruent‐low and incongruent‐high conditions. Consistent with the behavioral results, the EEG results revealed that N2 and P3 were sensitive to conflict strength. Critically, there were typical conflict adaptations between every two conflict conditions on the early P3 amplitude related to the adjustment of attentional strategies. However, there were no differences among these conflict adaptation effects, both on reaction times and the early P3 amplitude, demonstrating that the expectancy of conflict strength rather than conflict strength per se may play a crucial role in conflict adaptation. Altogether, these results emphasize the functional role of expectancy based on previous conflict strength in the exertion of cognitive control, which is in accordance with the repetition expectation theory than with the conflict monitoring theory.
Awareness of HLA‐B* 15:02 screening in trigeminal neuralgia and the gene screening policy among dentists in Southern Thailand
Authors: Saepoo Jirayu , Pangsomboon Kanokporn , Tianviwat Sukanya
Published: August 2022

Objectives

To determine the factors associated with public hospital dentists’ awareness of HLA‐B*15:02 screening in trigeminal neuralgia (TN) and the national gene screening policy in Thailand.

Methods

Cross‐sectional study. A validated questionnaire was distributed to public hospital dentists with at least 1 year of practice in Southern Thailand (n = 760) to assess their knowledge of TN, carbamazepine (CBZ) use, awareness of HLA‐B*15:02 screening, and the gene screening policy.

Results

A total of 385 dentists participated (50.7% response rate); 81.3% of respondents were aware of HLA‐B*15:02 screening. However, 18.7% of dentists were not aware of the importance of gene testing. Furthermore, dentists who were aware of gene screening had significantly better knowledge of TN diagnosis and CBZ use than “unaware” dentists. Awareness of HLA‐B*15:02 screening was also significantly associated with dental specialty. Moreover, 80.5% of respondents were not aware of the gene screening policy. The primary problems related to the policy were its inefficient publication, poor implementation, and lack of clinical practice guidelines (CPGs) to encourage dentists to follow the policy and prescribe gene tests.

Conclusion

While most hospital dentists were aware of the necessity of HLA‐B*15:02 screening prior to prescribing CBZ in TN, the majority were unaware of the national gene screening policy. Dental specialty and knowledge were associated with awareness of HLA‐B*15:02 screening.
Wh quantifier float in German
Authors: Doliana Aaron
Published: August 2022

This article investigates the syntactic distribution of the German quantificational particle known as “invariantalles” (‘all’). The generalization that emerges is that, given a derivation,allesoccurs in any position occupied by an Ā chain link of the “associate” ofalles, that is, the phrase thatalles“modifies.” The article concludes thatallesforms a deep constituent with its associate and that therefore instances of nonadjacentallesare derived transformationally, specifically by somestrandingprocedure.Floatinganalyses andadverbialanalyses of quantifier float are argued to be insufficient to explain the generalization. Three types of argument are presented in support: (a) the distribution ofallesis a subset of its associate's; (b)allesblocks derivations when it occurs in a position in which its associate would also block the derivation; (c)allesis sensitive to the kind of movement that its associate undergoes, in that it can occur in tails of Ā movement but not in tails of A movement. Further implications are thatwh movement proceeds successive‐cyclically through (presumably) vP in German, that tails of A and Ā movement can be distinguished byalles, and that object scrambling is necessarily A movement in German.
The effect of a large‐scale water, sanitation and hygiene intervention in Bangladesh on knowledge, behaviour and health: Findings from an endline programme evaluation
Authors: Aluri Kelly Zhang , Halder Amal K. , Islam Mahfuza , Benjamin‐Chung Jade , Alam Monirul , Shoab Abul Kasham , Rahman Mahbubur , Unicomb Leanne , Luby Stephen P.
Published: August 2022

Objectives

The Sanitation, Hygiene Education and Water Supply in Bangladesh Programme (SHEWA‐B) was a 5‐year intervention aiming to improve water, sanitation and hygiene (WASH) practices among 20 million rural residents through community hygiene promoters. This analysis evaluates the impact of SHEWA‐B on knowledge, behaviour and childhood diarrhoea outcomes.

Methods

The evaluation included repeated cross‐sectional surveys and health surveillance in matched cohorts in intervention and control clusters. Cross‐sectional surveys and structured observations at baseline, midline, and endline assessed the availability of WASH technology, caregiver knowledge and behaviour. Fieldworkers collected monthly health data in a subset of control and intervention households to determine the prevalence of diarrhoea.

Results

Of 5091 households surveyed, participants residing in intervention clusters showed minimal improvements in knowledge, reported behaviour, or use of WASH technology compared to the control clusters. During structured observations, intervention households increased more than control households at handwashing before preparing food and after cleaning a baby's anus when comparing endline to baseline, but these changes were not seen when comparing endline to the midline. The prevalence of childhood diarrhoea remained similar in both groups before (10.2% in intervention, 10.0% in control) and after (8.8% in intervention, 11.7% in control) midline changes were made to improve the intervention. Intervention clusters showed no improvement in diarrhoea over time compared to control clusters.

Conclusions

SHEWA‐B's community‐based WASH promotion did not yield the intended impact on knowledge, behaviour or health. Greater priority should be given to approaches that have demonstrated effectiveness. Including rigorous evaluations would broaden the evidence base to support and improve large‐scale programmes.
The ketogenic diet prevents steatosis and insulin resistance by reducing lipogenesis, diacylglycerol accumulation and protein kinase C activity in male rat liver
Authors: Jani Shailee , Da Eira Daniel , Stefanovic Mateja , Ceddia Rolando B.
Published: August 2022

Obesity‐associated insulin resistance plays a major role in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). The accumulation of diacylglycerol (DAG), ceramides and inflammation are key factors that cause NAFLD. In recent years, the ketogenic diet (KD) has emerged as an effective non‐pharmacological intervention for the treatment of NAFLD and other obesity‐related metabolic disorders. What remains undetermined is how the KD affects DAG and ceramide content and insulin sensitivity in the liver. Thus, this research was designed to assess these variables, as well as glucose and fat metabolism and markers of inflammation in livers of rats exposed for 8 weeks to one of the following diets: standard chow (SC), obesogenic high‐fat, sucrose‐enriched diet (HFS) or a KD. Despite having a higher fat content than the HFS diet, the KD did not cause steatosis and preserved hepatic insulin signalling. The KD reduced DAG content and protein kinase C‐ε activity, but markedly increased liver ceramide content. However, whereas the KD increased ceramide synthase 2 (CerS2) expression, it suppressed CerS6 expression, an effect that promoted the production of beneficial very long‐chain ceramides instead of harmful long‐chain ceramides. The KD also enhanced the liver expression of key genes involved in mitochondrial biogenesis and fatty acid oxidation (Pgc‐1α and Fgf21), suppressed inflammatory genes (Tnfα, Nf‐kb, Tlr4 and Il6), and shifted substrate away from de novo lipogenesis. Thus, through multiple mechanisms the KD exerted anti‐steatogenic and insulin‐sensitizing effects in the liver, which supports the use of this dietary intervention to treat NAFLD.

image

Key points

The accumulation of diacylglycerol (DAG), ceramides and inflammation are key factors that cause insulin resistance and non‐alcoholic fatty liver disease (NAFLD). This study provides evidence that a ketogenic diet (KD) rich in fat and devoid of carbohydrate reduced DAG content and preserved insulin signalling in the liver.

The KD shifted metabolism away from lipogenesis by enhancing genes involved in mitochondrial biogenesis and fatty acid oxidations in the liver.

The KD also promoted the production of beneficial very long‐chain ceramides instead of potentially harmful long‐chain ceramides.

Through multiple mechanisms, the KD exerted anti‐steatogenic and insulin‐sensitizing effects in the liver, which supports the use of this dietary intervention to treat NAFLD.
Análisis bibliométrico de la producción científica en violencia de género desde 2008 a 2018 en Iberoamérica
Authors: Estebarán Viñas Laura , González Sala Francisco , Tortosa-Pérez Macarena
Published: August 2022

Partiendo de un análisis bibliométrico de la literatura científica sobre violencia de género, el objetivo del presente estudio es analizar la producción científica en violencia de género de autores adscritos a instituciones españolas e iberoamericanas durante el período 2008 y 2018. A partir de la metodología PRISMA, se seleccionaron un total de 1455 artículos publicados en las bases de datos Web of Science Colección Principal, SciELO Citation Index y MEDLINE. Los resultados indican un aumento en la producción de artículos con los años, una mayor presencia de mujeres como firmantes y entre las grandes productoras, siendo los artículos firmados en colaboración por mujeres y hombres los más frecuentes, si bien son las mujeres las que con mayor frecuencia aparecen como primeras firmantes. Destaca una notable presencia de investigadoras españolas y brasileñas como las más productivas, siendo 27 revistas las responsables de publicar un 47.5 % de los artículos, entre las cuales destacan las revistas brasileñas. Se puede concluir la relevancia que tienen los estudios sobre violencia de género en la investigación iberoamericana.
Real-Time Reconfiguration Planning for the Dynamic Control of Reconfigurable Cable-Driven Parallel Robots
Authors: Xiong Hao , Cao Huanhui , Zeng Weifeng , Huang Junchang , Diao Xiumin , Lu Wenjie , Lou Yunjiang
Published: August 2022

The movable anchor points make reconfigurable cable-driven parallel robots (RCDPRs) advantageous over conventional cable-driven parallel robots with fixed anchor points, but the movable anchor points also introduce an inherent problem—reconfiguration planning. Scholars have proposed reconfiguration planning approaches for RCDPRs, taking into account the statics and kinematics of RCDPRs. However, a real-time reconfiguration planning approach that considers the dynamics of an RCDPR and is computationally efficient enough to be integrated into the RCDPR's dynamic controller is still not available in the literature yet. This paper develops a real-time reconfiguration planning approach for RCDPRs. A novel reconfiguration value function is defined to reflect the “value” of an RCDPR configuration and provide a reference index for the reconfiguration planning of an RCDPR. And then, the developed approach conducts reconfiguration planning based on the value of RCDPR configurations. The developed approach is computationally efficient, reducing the reconfiguration planning time by more than 93%, compared to single iteration of a box-constrained optimization-based reconfiguration planning approach. Such a high efficiency allows the developed approach to be integrated into an RCDPR's dynamic controller that usually runs with a high frequency. Integrating reconfiguration planning and dynamic control enhances the control performance of the RCDPR. To verify the effectiveness of the developed approach and the integration of reconfiguration planning and dynamic control for RCDPRs, a case study of an RCDPR with seven cables and four movable anchor points is conducted.
Cooling Characteristic of an Infrared Suppression Device With Single Perforated Funnel: A Computational Fluid Dynamics Approach
Authors: Mohanty Aurovinda , Senapati Santosh Kumar , Dash Manoj Kumar
Published: August 2022

An infrared suppression (IRS) device is integral to any gas turbine used in naval and cargo ships. Estimating an IRS device’s cooling characteristics is essential to start the maintenance operation. Thus, this article presents a computational investigation of the cooling characteristics of an infrared suppression device with a single cylindrical funnel with or without circular perforations. All simulations have been carried out in a steady and laminar environment. The numerical procedure adopted in this work has been validated with the existing correlations and achieved satisfactory agreement. The effect of the Rayleigh number and the length-to-diameter ratio of the funnel have been varied within the practical range to observe their effects on the averaged Nusselt number, heat transfer rate, mass suction rate, velocity fields, and thermal plumes. Moreover, the cooling performance has been compared for funnels without and with circular perforations. It is observed that the average Nu and the heat transfer rate increase with an increase in the Ra. Conversely, the average Nu first increases and then reduces with an increase in L/D. On the contrary, the heat transfer rate decreases monotonically with an increase in the L/D. The suction of fresh air into the funnel increases with Ra, whereas it reduces with an increase in L/D. The perforated funnels have better heat dissipation capacity than the unperforated ones.
Refrigerant flow distribution research for battery cooling coupled with cabin comfort based on dual-evaporator heat pump system for electric vehicle acceleration
Authors: Wang Yan , Wang Hewu , Gao Qing , Zhang Xiaohang , Zhang Xilong , Liu Zunmin
Published: August 2022

The heat pump system employed with a dual evaporator for battery cooling coupled with cabin comfort is an innovative thermal management method. It can be inferred that the refrigerant thermal load distribution can trigger temperature fluctuations for thermal performance of both battery and cabin. To trade-off between the thermal management demands of battery and cabin, this study proposed a strategy to promote the decreasing of battery temperature and to ensure battery thermal uniformity with a higher priority. Hence a transient refrigerant flow rate distribution scheme with a minimum flow rate to satisfy battery thermal demands was designed. The results showed a significant reduction in the temperature fluctuations for cabin thermal comfort and BTM thermal controlling. It offers a satisfactory reference for refrigerant thermal load distribution strategy applied with the heat pump system connected to the battery and cabin by the dual evaporator.
TV and video game streaming with a quantum receiver: A study on a Rydberg atom-based receiver's bandwidth and reception clarity
Authors: Prajapati Nikunjkumar , Rotunno Andrew P. , Berweger Samuel , Simons Matthew T. , Artusio-Glimpse Alexandra B. , Voran Stephen D. , Holloway Christopher L.
Published: August 2022

We demonstrate the ability to receive live color analog television and video game signals with the use of the Rydberg atom receiver. The typical signal expected for traditional 480i National Television Standards Committee format video signals requires a bandwidth of over 3 MHz. We determine the beam sizes, powers, and detection method required for the Rydberg atoms to receive this type of signal. The beam size affects the average time the atoms remain in the interaction volume, which is inversely proportional to the bandwidth of the receiver. We find that small beam diameters (less than 100 μm) lead to much faster responses and allow for color reception. We demonstrate the effect of the beam size on bandwidth by receiving a live 480i video stream with the Rydberg atom receiver. The best video reception was achieved with a beam width of 85 μm full-width at half-max.
A conserved long-distance telomeric silencing mechanism suppresses mTOR signaling in aging human fibroblasts
Authors: Jäger Kathrin , Mensch Juliane , Grimmig Maria Elisabeth , Neuner Bruno , Gorzelniak Kerstin , Türkmen Seval , Demuth Ilja , Hartmann Alexander , Hartmann Christiane , Wittig Felix , Sporbert Anje , Hermann Andreas , Fuellen Georg , Möller Steffen , Walter Michael
Published: August 2022

Telomeres are repetitive nucleotide sequences at the ends of each chromosome. It has been hypothesized that telomere attrition evolved as a tumor suppressor mechanism in large long-lived species. Long telomeres can silence genes millions of bases away through a looping mechanism called telomere position effect over long distances (TPE-OLD). The function of this silencing mechanism is unknown. We determined a set of 2322 genes with high positional conservation across replicatively aging species that includes known and candidate TPE-OLD genes that may mitigate potentially harmful effects of replicative aging. Notably, we identified
PPP2R2C
as a tumor suppressor gene, whose up-regulation by TPE-OLD in aged human fibroblasts leads to dephosphorylation of p70S6 kinase and mammalian target of rapamycin suppression. A mechanistic link between telomeres and a tumor suppressor mechanism supports the hypothesis that replicative aging fulfills a tumor suppressor function and motivates previously unknown antitumor and antiaging strategies.
Moiré metasurfaces for dynamic beamforming
Authors: Liu Shuo , Ma Shaojie , Shao Ruiwen , Zhang Lei , Yan Tao , Ma Qian , Zhang Shuang , Cui Tie Jun
Published: August 2022

Recent advances in digitally programmable metamaterials have accelerated the development of reconfigurable intelligent surfaces (RIS). However, the excessive use of active components (e.g., pin diodes and varactor diodes) leads to high costs, especially for those operating at millimeter-wave frequencies, impeding their large-scale deployments in RIS. Here, we introduce an entirely different approach—moiré metasurfaces—to implement dynamic beamforming through mutual twists of two closely stacked metasurfaces. The superposition of two high-spatial-frequency patterns produces a low-spatial-frequency moiré pattern through the moiré effect, which provides the surface impedance profiles to generate desired radiation patterns. We demonstrate experimentally that the direction of the radiated beams can continuously sweep over the entire reflection space along predesigned trajectories by simply adjusting the twist angle and the overall orientation. Our work opens previously unexplored directions for synthesizing far-field scattering through the direct contact of mutually twisted metallic patterns with different plane symmetry groups.
Complement C3 inhibition in severe COVID-19 using compstatin AMY-101
Authors: Skendros Panagiotis , Germanidis Georgios , Mastellos Dimitrios C. , Antoniadou Christina , Gavriilidis Efstratios , Kalopitas Georgios , Samakidou Anna , Liontos Angelos , Chrysanthopoulou Akrivi , Ntinopoulou Maria , Kogias Dionysios , Karanika Ioanna , Smyrlis Andreas , Cepaityte Dainora , Fotiadou Iliana , Zioga Nikoleta , Mitroulis Ioannis , Gatselis Nikolaos K. , Papagoras Charalampos , Metallidis Simeon , Milionis Haralampos , Dalekos George N. , Willems Loek , Persson Barbro , Manivel Vivek Anand , Nilsson Bo , Connolly E. Sander , Iacobelli Simona , Papadopoulos Vasileios , Calado Rodrigo T. , Huber-Lang Markus , Risitano Antonio M. , Yancopoulou Despina , Ritis Konstantinos , Lambris John D.
Published: August 2022

Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 (
n
= 16) or placebo (
n
= 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101–treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug’s inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.
Developmental basis of evolutionary lung loss in plethodontid salamanders
Authors: Lewis Zachary R. , Kerney Ryan , Hanken James
Published: August 2022

One or more members of four living amphibian clades have independently dispensed with pulmonary respiration and lack lungs, but little is known of the developmental basis of lung loss in any taxon. We use morphological, molecular, and experimental approaches to examine the Plethodontidae, a dominant family of salamanders, all of which are lungless as adults. We confirm an early anecdotal report that plethodontids complete early stages of lung morphogenesis: Transient embryonic lung primordia form but regress by apoptosis before hatching. Initiation of pulmonary development coincides with expression of the lung-specification gene
Wnt2b
in adjacent mesoderm, and the lung rudiment expresses pulmonary markers
Nkx2.1
and
Sox9
. Lung developmental-genetic pathways are at least partially conserved despite the absence of functional adult lungs for at least 25 and possibly exceeding 60 million years. Adult lung loss appears associated with altered expression of signaling molecules that mediate later stages of tracheal and pulmonary development.
A synthetic biology approach reveals diverse and dynamic CDK response profiles via multisite phosphorylation of NLS-NES modules
Authors: Faustova Ilona , Örd Mihkel , Kiselev Viacheslav , Fedorenko Dmytro , Borovko Irina , Macs Dags , Pääbo Kaur , Lõoke Marko , Loog Mart
Published: August 2022

The complexity of multisite phosphorylation mechanisms in regulating nuclear localization signals (NLSs) and nuclear export signals (NESs) is not understood, and its potential has not been used in synthetic biology. The nucleocytoplasmic shuttling of many proteins is regulated by cyclin-dependent kinases (CDKs) that rely on multisite phosphorylation patterns and short linear motifs (SLiMs) to dynamically control proteins in the cell cycle. We studied the role of motif patterns in nucleocytoplasmic shuttling using sensors based on the CDK targets Dna2, Psy4, and Mcm2/3 of
Saccharomyces cerevisiae
. We designed multisite phosphorylation modules by rearranging phosphorylation sites, cyclin-specific SLiMs, phospho-priming, phosphatase specificity, and NLS/NES phospho-regulation and obtained very different substrate localization dynamics. These included ultrasensitive responses with and without a delay, graded responses, and different homeostatic plateaus. Thus, CDK can do much more than trigger sequential switches during the cell cycle as it can drive complex patterns of protein localization and activity by using multisite phosphorylation networks.
Data for all: Tactile graphics that light up with picture-perfect resolution
Authors: Koone Jordan C. , Dashnaw Chad M. , Alonzo Emily A. , Iglesias Miguel A. , Patero Kelly-Shaye , Lopez Juan J. , Zhang Ao Yun , Zechmann Bernd , Cook Noah E. , Minkara Mona S. , Supalo Cary A. , Wedler Hoby B. , Guberman-Pfeffer Matthew J. , Shaw Bryan F.
Published: August 2022

People who are blind do not have access to graphical data and imagery produced by science. This exclusion complicates learning and data sharing between sighted and blind persons. Because blind people use tactile senses to visualize data (and sighted people use eyesight), a single data format that can be easily visualized by both is needed. Here, we report that graphical data can be three-dimensionally printed into tactile graphics that glow with video-like resolution via the lithophane effect. Lithophane forms of gel electropherograms, micrographs, electronic and mass spectra, and textbook illustrations could be interpreted by touch or eyesight at ≥79% accuracy (
n
= 360). The lithophane data format enables universal visualization of data by people regardless of their level of eyesight.
Inhibiting intercrystalline reactions of anode with electrolytes for long-cycling lithium batteries
Authors: Shi Peng , Fu Zhong-Heng , Zhou Ming-Yue , Chen Xiang , Yao Nan , Hou Li-Peng , Zhao Chen-Zi , Li Bo-Quan , Huang Jia-Qi , Zhang Xue-Qiang , Zhang Qiang
Published: August 2022

The life span of lithium batteries as energy storage devices is plagued by irreversible interfacial reactions between reactive anodes and electrolytes. Occurring on polycrystal surface, the reaction process is inevitably affected by the surface microstructure of anodes, of which the understanding is imperative but rarely touched. Here, the effect of grain boundary of lithium metal anodes on the reactions was investigated. The reactions preferentially occur at the grain boundary, resulting in intercrystalline reactions. An aluminum (Al)–based heteroatom-concentrated grain boundary (Al-HCGB), where Al atoms concentrate at grain boundary, was designed to inhibit the intercrystalline reactions. In particular, the scalable preparation of Al-HCGB was demonstrated, with which the cycling performance of a pouch cell (355 Wh kg
−1
) was significantly improved. This work opens a new avenue to explore the effect of the surface microstructure of anodes on the interfacial reaction process and provides an effective strategy to inhibit reactions between anodes and electrolytes for long–life-span practical lithium batteries.
Sphingosine 1-phosphate signaling in perivascular cells enhances inflammation and fibrosis in the kidney
Authors: Tanaka Shinji , Zheng Shuqiu , Kharel Yugesh , Fritzemeier Russell G. , Huang Tao , Foster Daniel , Poudel Nabin , Goggins Eibhlin , Yamaoka Yusuke , Rudnicka Kinga P. , Lipsey Jonathan E. , Radel Hope V. , Ryuh Sophia M. , Inoue Tsuyoshi , Yao Junlan , Rosin Diane L. , Schwab Susan R. , Santos Webster L. , Lynch Kevin R. , Okusa Mark D.
Published: August 2022

Chronic kidney disease (CKD), characterized by sustained inflammation and progressive fibrosis, is highly prevalent and can eventually progress to end-stage kidney disease. However, current treatments to slow CKD progression are limited. Sphingosine 1-phosphate (S1P), a product of sphingolipid catabolism, is a pleiotropic mediator involved in many cellular functions, and drugs targeting S1P signaling have previously been studied particularly for autoimmune diseases. The primary mechanism of most of these drugs is functional antagonism of S1P receptor-1 (S1P1) expressed on lymphocytes and the resultant immunosuppressive effect. Here, we documented the role of local S1P signaling in perivascular cells in the progression of kidney fibrosis using primary kidney perivascular cells and several conditional mouse models. S1P was predominantly produced by sphingosine kinase 2 in kidney perivascular cells and exported via spinster homolog 2 (Spns2). It bound to S1P1 expressed in perivascular cells to enhance production of proinflammatory cytokines/chemokines upon injury, leading to immune cell infiltration and subsequent fibrosis. A small-molecule Spns2 inhibitor blocked S1P transport, resulting in suppression of inflammatory signaling in human and mouse kidney perivascular cells in vitro and amelioration of kidney fibrosis in mice. Our study provides insight into the regulation of inflammation and fibrosis by S1P and demonstrates the potential of Spns2 inhibition as a treatment for CKD and potentially other inflammatory and fibrotic diseases that avoids the adverse events associated with systemic modulation of S1P receptors.
Widespread cell stress and mitochondrial dysfunction occur in patients with early Alzheimer’s disease
Authors: Venkataraman Ashwin V. , Mansur Ayla , Rizzo Gaia , Bishop Courtney , Lewis Yvonne , Kocagoncu Ece , Lingford-Hughes Anne , Huiban Mickael , Passchier Jan , Rowe James B. , Tsukada Hideo , Brooks David J. , Martarello Laurent , Comley Robert A. , Chen Laigao , Schwarz Adam J. , Hargreaves Richard , Gunn Roger N. , Rabiner Eugenii A. , Matthews Paul M.
Published: August 2022

Cell stress and impaired oxidative phosphorylation are central to mechanisms of synaptic loss and neurodegeneration in the cellular pathology of Alzheimer’s disease (AD). In this study, we quantified the in vivo expression of the endoplasmic reticulum stress marker, sigma 1 receptor (S1R), using [
11
C]SA4503 positron emission tomography (PET), the mitochondrial complex I (MC1) with [
18
F]BCPP-EF, and the presynaptic vesicular protein SV2A with [
11
C]UCB-J in 12 patients with early AD and in 16 cognitively normal controls. We integrated these molecular measures with assessments of regional brain volumes and cerebral blood flow (CBF) measured with magnetic resonance imaging arterial spin labeling. Eight patients with AD were followed longitudinally to estimate the rate of change of the physiological and structural pathology markers with disease progression. The patients showed widespread increases in S1R (≤ 27%) and regional reduction in MC1 (≥ −28%) and SV2A (≥ −25%) radioligand binding, brain volume (≥ −23%), and CBF (≥ −26%). [
18
F]BCPP-EF PET MC1 binding (≥ −12%) and brain volumes (≥ −5%) showed progressive reductions over 12 to 18 months, suggesting that they both could be used as pharmacodynamic indicators in early-stage therapeutics trials. Associations of reduced MC1 and SV2A and increased S1R radioligand binding with reduced cognitive performance in AD, although exploratory, suggested a loss of metabolic functional reserve with disease. Our study thus provides in vivo evidence for widespread, clinically relevant cellular stress and bioenergetic abnormalities in early AD.
The systemic anti-microbiota IgG repertoire can identify gut bacteria that translocate across gut barrier surfaces
Authors: Vujkovic-Cvijin Ivan , Welles Hugh C. , Ha Connie W. Y. , Huq Lutfi , Mistry Shreni , Brenchley Jason M. , Trinchieri Giorgio , Devkota Suzanne , Belkaid Yasmine
Published: August 2022

Unique gut microbiota compositions have been associated with inflammatory diseases, but identifying gut bacterial functions linked to immune activation in humans remains challenging. Translocation of pathogens from mucosal surfaces into peripheral tissues can elicit immune activation, although whether and which gut commensal bacteria translocate in inflammatory diseases is difficult to assess. We report that a subset of commensal gut microbiota constituents that translocate across the gut barrier in mice and humans are associated with heightened systemic immunoglobulin G (IgG) responses. We present a modified high-throughput, culture-independent approach to quantify systemic IgG against gut commensal bacteria in human serum samples without the need for paired stool samples. Using this approach, we highlight several commensal bacterial species that elicit elevated IgG responses in patients with inflammatory bowel disease (IBD) including taxa within the clades
Collinsella
,
Bifidobacterium
,
Lachnospiraceae
, and
Ruminococcaceae
. These and other taxa identified as translocating bacteria or targets of systemic immunity in IBD concomitantly exhibited heightened transcriptional activity and growth rates in IBD patient gut microbiomes. Our approach represents a complementary tool to illuminate interactions between the host and its gut microbiota and may provide an additional method to identify microbes linked to inflammatory disease.
Durable protection against the SARS-CoV-2 Omicron variant is induced by an adjuvanted subunit vaccine
Authors: Arunachalam Prabhu S. , Feng Yupeng , Ashraf Usama , Hu Mengyun , Walls Alexandra C. , Edara Venkata Viswanadh , Zarnitsyna Veronika I. , Aye Pyone Pyone , Golden Nadia , Miranda Marcos C. , Green Kristyn W. M. , Threeton Breanna M. , Maness Nicholas J. , Beddingfield Brandon J. , Bohm Rudolf P. , Scheuermann Sarah E. , Goff Kelly , Dufour Jason , Russell-Lodrigue Kasi , Kepl Elizabeth , Fiala Brooke , Wrenn Samuel , Ravichandran Rashmi , Ellis Daniel , Carter Lauren , Rogers Kenneth , Shirreff Lisa M. , Ferrell Douglas E. , Deb Adhikary Nihar R. , Fontenot Jane , Hammond Holly L. , Frieman Matthew , Grifoni Alba , Sette Alessandro , O’Hagan Derek T. , Van Der Most Robbert , Rappuoli Rino , Villinger Francois , Kleanthous Harry , Rappaport Jay , Suthar Mehul S. , Veesler David , Wang Taia T. , King Neil P. , Pulendran Bali
Published: August 2022

Despite the remarkable efficacy of COVID-19 vaccines, waning immunity and the emergence of SARS-CoV-2 variants such as Omicron represents a global health challenge. Here, we present data from a study in nonhuman primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine comprising the receptor binding domain of the ancestral strain (RBD-Wu) on the I53-50 nanoparticle adjuvanted with AS03, which was recently authorized for use in individuals 18 years or older. Vaccination induced neutralizing antibody (nAb) titers that were maintained at high concentrations for at least 1 year after two doses, with a pseudovirus nAb geometric mean titer (GMT) of 1978 and a live virus nAb GMT of 1331 against the ancestral strain but not against the Omicron BA.1 variant. However, a booster dose at 6 to 12 months with RBD-Wu or RBD-β (RBD from the Beta variant) displayed on I53-50 elicited high neutralizing titers against the ancestral and Omicron variants. In addition, we observed persistent neutralization titers against a panel of sarbecoviruses, including SARS-CoV. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Vaccination resulted in protection against Omicron infection in the lung and suppression of viral burden in the nares at 6 weeks after the final booster immunization. Even at 6 months after vaccination, we observed protection in the lung and rapid control of virus in the nares. These results highlight the durable and cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine.
Loss of Pfizer (BNT162b2) Vaccine-Induced Antibody Responses against the SARS-CoV-2 Omicron Variant in Adolescents and Adults
Authors: Gupta Sneh Lata , Mantus Grace , Manning Kelly E. , Ellis Madison , Patel Mit , Ciric Caroline Rose , Lu Austin , Turner Jackson S. , O’Halloran Jane A. , Presti Rachel M. , Joshi Devyani Jaideep , Ellebedy Ali H. , Anderson Evan J. , Rostad Christina A. , Suthar Mehul S. , Wrammert Jens
Published: August 2022

While plasma binding and neutralizing antibody responses have been reported for cohorts of infected and vaccinated adults, much less is known about the vaccine-induced antibody responses to variants including Omicron in children. This illustrates the need to characterize vaccine efficacy in key vulnerable populations.
Herpes Simplex Virus Type 1 Preferentially Enhances Neuro-Inflammation and Senescence in Brainstem of Female Mice
Authors: Sivasubramanian Mahesh Kumar , Monteiro Raisa , Harrison Kelly S. , Plakkot Bhuvana , Subramanian Madhan , Jones Clinton
Published: August 2022

HSV-1 (herpes simplex virus 1), an important human pathogen, establishes lifelong latency in neurons in trigeminal ganglia and the central nervous system. In contrast to productive infection, the only viral transcript abundantly expressed in latently infected neurons is the latency associated transcript (LAT).
Metagenome-Assembled Genome Sequence of Marine
Rhizobiaceae
sp. Strain MnEN-MB40S, Obtained from Manganese-Oxidizing Enrichment Culture
Authors: Aoki Masataka , Nakahara Nozomi , Kusube Masataka , Syutsubo Kazuaki
Published: August 2022

Here, we report a new metagenome-assembled genome (MAG) from a marine
Rhizobiaceae
species. The MnEN-MB40S genome was assembled from a manganese-oxidizing enrichment culture metagenome. A 4.1-Mb MAG comprising 26 contigs, with a GC content of 60.0%, was obtained. This MAG contributes to the genomic information regarding the family
Rhizobiaceae
.
Unique Insights into How Plants and Soil Microbiomes Interact Are at Our Fingertips
Authors: Armengaud Jean
Published: August 2022

Global warming endangers our world, with probably a drastic drop in food production as one of the first vital consequences for humanity. To maintain or improve quality and sustainable yields, the burning imperative for agriculture is to rapidly integrate the essential component for plant development and soil regeneration, namely, the soil microbiome.
A Novel Triple Combination To Combat Serious Infections with Carbapenem-Resistant Acinetobacter baumannii in a Mouse Pneumonia Model
Authors: Al-Madboly Lamiaa A.
Published: August 2022

Combination therapy provides a perspective to threat multidrug-resistant (MDR) strains. The present study sheds light on a novel and effective triple combination against carbapenem-resistant
A. baumannii
.