bluuebunny/crossref_metadata_2025 huggingface dataset:
Resolving exit strategies of mycobacteria in Dictyostelium discoideum by combining high‐pressure freezing with 3D‐correlative light and electron microscopy
Authors: Franzkoch Rico , Anand Aby , Breitsprecher Leonhard , Psathaki Olympia E. , Barisch Caroline
Published: December 2023

The infection course of Mycobacterium tuberculosis is highly dynamic and comprises sequential stages that require damaging and crossing of several membranes to enable the translocation of the bacteria into the cytosol or their escape from the host. Many important breakthroughs such as the restriction of mycobacteria by the autophagy pathway and the recruitment of sophisticated host repair machineries to the Mycobacterium‐containing vacuole have been gained in the Dictyostelium discoideum/M. marinum system. Despite the availability of well‐established light and advanced electron microscopy techniques in this system, a correlative approach integrating both methods with near‐native ultrastructural preservation is currently lacking. This is most likely due to the low ability of D. discoideum to adhere to surfaces, which results in cell loss even after fixation. To address this problem, we improved the adhesion of cells and developed a straightforward and convenient workflow for 3D‐correlative light and electron microscopy. This approach includes high‐pressure freezing, which is an excellent technique for preserving membranes. Thus, our method allows to monitor the ultrastructural aspects of vacuole escape which is of central importance for the survival and dissemination of bacterial pathogens.
Comparing the diagnostic accuracy of PCR‐reverse blot hybridization assay and conventional fungus study in superficial fungal infection of the skin: A systematic review
Authors: Jeon Jae Joon , Kim You Hyun , Lim Sung Ha , Lee Solam , Choi Eung Ho
Published: December 2023

Background

In superficial fungal infections, prompt diagnosis and treatment are essential to prevent the spread of infection and minimise the impact on patients' quality of life. Traditional diagnostic methods, such as KOH smear and fungal culture, have limitations in terms of sensitivity and turnaround time. Recently, the PCR‐reverse blot hybridization assay (PCR‐REBA) has been developed for the direct detection of dermatophyte DNA. However, there is a lack of information assessing the diagnostic accuracy of PCR‐REBA.

Objectives

This systematic review aimed to evaluate the diagnostic accuracy of PCR‐REBA in superficial fungal infections compared to conventional and molecular methods.

Methods

The comprehensive search containing Ovid MEDLINE and Embase databases was conducted on 7 August 2022. Two reviewers independently reviewed the included articles. Quality assessment was performed using the Newcastle‐Ottawa Scale tool.

Results

The included studies were conducted in Korea (five studies) and the Netherlands (two studies), all of which were conducted in a single institution. The quality assessment of these studies indicated low risk of bias. When compared to the potassium hydroxide (KOH) smear and fungus culture, the sensitivity of PCR‐REBA ranged from 85% to 100%, and the positive predictive values ranged from 58.9% to 100%. When compared to the RT‐PCR, the sensitivity of PCR‐REBA ranged from 93.3% to 100%, and the positive and negative predictive values were 91.6%–99.6% and 81.0%–89.1%, respectively.

Conclusions

The PCR‐REBA shows promise as a valuable diagnostic tool for dermatophytosis, offering practical and cost‐effective benefits.
The accuracy of radial artery applanation tonometry and intra‐arterial blood pressure monitoring in critically ill patients: An evidence‐based review
Authors: Borg Amber Leigh , Trapani Josef
Published: December 2023

The invasive intra‐arterial approach is the gold standard for measuring blood pressure in intensive care units where accuracy is crucial. However, invasive procedures increase the risk of infections and mortality. This evidence‐based review aimed to determine whether continuous non‐invasive blood pressure (CNIBP) monitoring, using Radial Artery Applanation Tonometry (RAAT) devices, is as accurate as invasive methods. Six papers were included: three prospective cohort studies and three comparative studies. Most studies showed that mean arterial pressure is accurately recorded through RAAT monitoring; however, more research is needed to assess the accuracy of non‐invasive readings of systolic and diastolic blood pressures, as data are not always concordant.
Extending the methodology of critical discourse analysis using Haraway's figurations: The example of The Monstrous Perpetrator within contemporary responses to child neglect and abuse
Authors: Einboden Rochelle , Varcoe Colleen , Rudge Trudy
Published: December 2023

Critical discursive analyses offer possibilities for equity‐oriented research, and are a resource for addressing resistant social problems, such as child neglect and abuse (CN&A). A key challenge for discourse analysts in health disciplines is the tensions between materiality and social constructions, particularly at the site of the body. This paper describes how Donna Haraway's ideas of figuration and technobiopower can augment critical discourse analysis to address this tension. Technobiopower, an intensification of biopower in the context of technoscience, is seen as underpinning the melding of material and semiotic practices. The subject is no longer a material body, but a hybrid body that exists in tropic figuration between the real and unreal. This paper uses an analysis of the figuration of The Monstrous Perpetrator from a study of nursing responses to CN&A to illustrate how Haraway's figuration aligns with and provides an analytical tool to extend critical discursive analyses. Specifically, this methodology offers new ways to identify the discursive qualities of bodies, and how material aspects of bodies are exaggerated, concealing their hegemonic ideologies and discriminatory effects. By identifying discourses within or inscribed upon the body, they can be disrupted, opening new possibilities for social change.
Regulation of Rubisco activity in crops
Authors: Amaral Joana , Lobo Ana K. M. , Carmo‐Silva Elizabete
Published: December 2023

Efficient plant acclimation to changing environmental conditions relies on fast adjustments of the transcriptome, proteome, and metabolome. Regulation of enzyme activity depends on the activity of specific chaperones, chemical post‐translational modifications (PTMs) of amino acid residues, and changes in the cellular and organellar microenvironment. Central to carbon assimilation, and thus plant growth and yield, Rubisco activity is regulated by its chaperone Rubisco activase (Rca) and by adjustments in the chloroplast stroma environment. Focused on crops, this review highlights the main PTMs and stromal ions and metabolites affecting Rubisco and Rca in response to environmental stimuli. Rca isoforms differ in regulatory properties and heat sensitivity, with expression changing according to the surrounding environment. Much of the physiological relevance of Rubisco and Rca PTMs is still poorly understood, though some PTMs have been associated with Rubisco regulation in response to stress. Ion and metabolite concentrations in the chloroplast change in response to variations in light and temperature. Some of these changes promote Rubisco activation while others inhibit activation, deactivate the enzyme, or change the rates of catalysis. Understanding these regulatory mechanisms will aid the development of strategies to improve carbon fixation by Rubisco under rapidly changing environments as experienced by crop plants.
Defective kernel 58 encodes an Rrp15p domain‐containing protein essential to ribosome biogenesis and seed development in maize
Authors: Ma Bing , Liu Hui , Xiu Zhi‐hui , Yang Huan‐huan , Wang Hongqiu , Wang Yong , Tan Bao‐Cai
Published: December 2023

Ribosome biogenesis is a highly dynamic and orchestrated process facilitated by hundreds of ribosomal biogenesis factors and small nucleolar RNAs. While many of the advances are derived from studies in yeast, ribosome biogenesis remains largely unknown in plants despite its importance to plant growth and development.

Through characterizing the maize (Zea mays) defective kernel and embryo‐lethal mutant dek58, we show that DEK58 encodes an Rrp15p domain‐containing protein with 15.3% identity to yeast Rrp15. Over‐expression of DEK58 rescues the mutant phenotype.

DEK58 is localized in the nucleolus. Ribosome profiling and RNA gel blot analyses show that the absence of DEK58 reduces ribosome assembly and impedes pre‐rRNA processing, accompanied by the accumulation of nearly all the pre‐rRNA processing intermediates and the production of an aberrant processing product P‐25S*. DEK58 interacts with ZmSSF1, a maize homolog of the yeast Ssf1 in the 60S processome. DEK58 and ZmSSF1 interact with ZmCK2α, a putative component of the yeast UTP‐C complex involved in the small ribosomal subunit processome.

These results demonstrate that DEK58 is essential to seed development in maize. It functions in the early stage of pre‐rRNA processing in ribosome biogenesis, possibly through interacting with ZmSSF1 and ZmCK2α in maize.
DNA methylation in the wild: epigenetic transgenerational inheritance can mediate adaptation in clones of wild strawberry (Fragaria vesca)
Authors: Sammarco Iris , Díez Rodríguez Bárbara , Galanti Dario , Nunn Adam , Becker Claude , Bossdorf Oliver , Münzbergová Zuzana , Latzel Vít
Published: December 2023

Due to the accelerating climate change, it is crucial to understand how plants adapt to rapid environmental changes. Such adaptation may be mediated by epigenetic mechanisms like DNA methylation, which could heritably alter phenotypes without changing the DNA sequence, especially across clonal generations. However, we are still missing robust evidence of the adaptive potential of DNA methylation in wild clonal populations.

Here, we studied genetic, epigenetic and transcriptomic variation of Fragaria vesca, a predominantly clonally reproducing herb. We examined samples from 21 natural populations across three climatically distinct geographic regions, as well as clones of the same individuals grown in a common garden.

We found that epigenetic variation was partly associated with climate of origin, particularly in non‐CG contexts. Importantly, a large proportion of this variation was heritable across clonal generations. Additionally, a subset of these epigenetic changes affected the expression of genes mainly involved in plant growth and responses to pathogen and abiotic stress. These findings highlight the potential influence of epigenetic changes on phenotypic traits.

Our findings indicate that variation in DNA methylation, which can be environmentally inducible and heritable, may enable clonal plant populations to adjust to their environmental conditions even in the absence of genetic adaptation.
A heat‐inducible expression system for external control of gene expression in plastids
Authors: Xu Wenbo , Li Shengchun , Bock Ralph , Zhang Jiang
Published: December 2023

Inducible expression systems can overcome the trade‐off between high‐level transgene expression and its pleiotropic effects on plant growth. In addition, they can facilitate the expression of biochemical pathways that produce toxic metabolites. Although a few inducible expression systems for the control of transgene expression in plastids have been developed, they all depend on chemical inducers and/or nuclear transgenes. Here we report a temperature‐inducible expression system for plastids that is based on the bacteriophage λ leftward and rightward promoters (pL/pR) and the temperature‐sensitive repressor cI857. We show that the expression of green fluorescent protein (GFP) in plastids can be efficiently repressed by cI857 under normal growth conditions, and becomes induced over time upon exposure to elevated temperatures in a light‐dependent process. We further demonstrate that by introducing into plastids an expression system based on the bacteriophage T7 RNA polymerase, the temperature‐dependent accumulation of GFP increased further and was ~24 times higher than expression driven by the pL/pR promoter alone, reaching ~0.48% of the total soluble protein. In conclusion, our heat‐inducible expression system provides a new tool for the external control of plastid (trans) gene expression that is cost‐effective and does not depend on chemical inducers.
Multi‐omics identification of a key glycosyl hydrolase gene FtGH1 involved in rutin hydrolysis in Tartary buckwheat (Fagopyrum tataricum)
Authors: Lai Dili , Zhang Kaixuan , He Yuqi , Fan Yu , Li Wei , Shi Yaliang , Gao Yuanfen , Huang Xu , He Jiayue , Zhao Hui , Lu Xiang , Xiao Yawen , Cheng Jianping , Ruan Jingjun , Georgiev Milen I. , Fernie Alisdair R. , Zhou Meiliang
Published: December 2023

Rutin, a flavonoid rich in buckwheat, is important for human health and plant resistance to external stresses. The hydrolysis of rutin to quercetin underlies the bitter taste of Tartary buckwheat. In order to identify rutin hydrolysis genes, a 200 genotypes mini‐core Tartary buckwheat germplasm resource was re‐sequenced with 30‐fold coverage depth. By combining the content of the intermediate metabolites of rutin metabolism with genome resequencing data, metabolite genome‐wide association analyses (GWAS) eventually identified a glycosyl hydrolase gene FtGH1, which could hydrolyse rutin to quercetin. This function was validated both in Tartary buckwheat overexpression hairy roots and in vitro enzyme activity assays. Mutation of the two key active sites, which were determined by molecular docking and experimentally verified via overexpression in hairy roots and transient expression in tobacco leaves, exhibited abnormal subcellular localization, suggesting functional changes. Sequence analysis revealed that mutation of the FtGH1 promoter in accessions of two haplotypes might be necessary for enzymatic activity. Co‐expression analysis and GWAS revealed that FtbHLH165 not only repressed FtGH1 expression, but also increased seed length. This work reveals a potential mechanism behind rutin metabolism, which should provide both theoretical support in the study of flavonoid metabolism and in the molecular breeding of Tartary buckwheat.
Overview of current melanoma therapies
Authors: Fateeva Anna , Eddy Kevinn , Chen Suzie
Published: December 2023

Melanoma is the most aggressive type of skin cancer and is responsible for the majority of deaths from skin cancer. Therapeutic advances in the last few decades, notably the development of novel targeted therapies and immunotherapies have significantly improved patient outcomes; nonetheless, these options remain limited due to the onset of resistance to treatment modalities and relapse. In this review, we focus on the available therapeutic options, their benefits, and limitations.
Christian nationalism, religious struggles, and the structural amplification of emotional distress
Authors: Upenieks Laura , Hill Terrence D.
Published: December 2023

Objective

Although studies have linked Christian nationalist beliefs with greater emotional distress, little is known about the potential underlying mechanisms or subgroup variations. Informed by the strain‐struggles‐distress model and the concept of structural amplification, we tested whether religious/spiritual (R/S) struggles mediate and moderate the association between Christian nationalist beliefs and emotional distress.

Methods

Regression models were conducted on national survey data collected in 2021 (n = 1704).

Results

Results suggested that respondents who reported stronger Christian nationalist beliefs also tended to report higher levels of R/S struggles, anger, and psychological distress. Mediation analyses revealed significant indirect effects of Christian nationalist beliefs on emotional distress through R/S struggles. Moderation analyses also indicated that the effects of Christian nationalist beliefs on emotional distress were amplified at higher levels of R/S struggles.

Conclusion

In support of the strain‐struggles‐distress and structural amplification models, we find that the adverse emotional impacts Christian nationalism are explained and intensified by the cognitive vulnerabilities of R/S struggles.
The effects of pen ink and surface disinfectants on red blood cells stored in plasticized polyvinylchloride transfusion bags
Authors: Uy Ralph Justin , Serrano Katherine , Hadjesfandiari Narges , Shih Andrew W. , Devine Dana
Published: December 2023

Background

Each unit of red blood cells (RBCs) produced represents a significant cost to the healthcare system. Unnecessary blood wastage should be minimized. In clinical settings, alterations to blood component bags after issue from the protected setting of the blood bank include pen markings, and those that are exposed to an infectious environment require surface disinfecting. These units may be discarded due to unclear effects on RBC quality. In this study, we investigate whether pen markings or surface disinfection negatively affects the quality of packed RBCs and whether pen ink diffuses through the blood bag.

Study Design and Methods

RBC bags were marked with pens (water, oil, or alcohol‐based) or subjected to surface disinfection (ethanol, hydrogen peroxide [Preempt wipes], or benzalkonium chloride‐based wipes [CaviWipes]) and sampled 24 h after applying the treatment and at day 42 post collection (n = 3 for each condition). The samples were analyzed for RBC in vitro quality markers. The presence of any ink in the RBC bags was investigated using mass spectrometry (n = 2).

Results

Data from 24 h and day 42 time points indicated no differences in RBC count, mean corpuscular volume, morphology, deformability, potassium content, or hemolysis for either pen markings or disinfectants when compared with their untreated controls (p > .05). No trace of ink was detected inside the bag.

Conclusion

RBC units marked with ballpoint, gel, or Sharpie pens do not suffer a loss of in vitro quality, nor do RBC units which have been surface disinfected with 70% ethanol, Preempt wipes or CaviWipes.
Galois actions of finitely generated groups rarely have model companions
Authors: Beyarslan Özlem , Kowalski Piotr
Published: December 2023

We show that if is a finitely generated group such that its profinite completion is “far from being projective” (i.e., the kernel of the universal Frattini cover of is not a small profinite group), then the class of existentially closed ‐actions on fields is not elementary. Since any infinite, finitely generated, virtually free, and not free group is “far from being projective,” the main result of this paper corrects an error in our paper, Beyarslan and Kowalski (Proc. London Math. Soc., (2) 118 (2019), 221–256), by showing the negation of Theorem 3.26 in that paper.
The reproducibility of dendritic cell and T cell counts to a 30‐min high‐intensity cycling protocol as a tool to highlight overtraining
Authors: Baker Carla , Piasecki Jessica , Hunt John A. , Hough John
Published: December 2023

Heavy training has been reported to be immunosuppressive in athletes and lead to blunted cortisol responses to exercise. Cortisol elevates the number of dendritic cells (DCs), key antigen‐presenting cells that interact with T cells to initiate an immune response. Reproducible cortisol responses to a 30‐min cycle test have been identified but were based on percentage of work rate maximum. To ensure physiological consistency, submaximal anchors, that is, ventilatory threshold (VT1) should prescribe intensity. This study aims to assess the reproducibility of the DC and T cell responses to an adapted stress test to assess its usefulness in assessing DC dysfunction with intensified training. Twelve males cycled for 1 min at 20% below VT1 and 4 min at 50% between VT1 and , for 30 min (20/50), with blood samples pre‐, post‐ and 30 min post‐exercise. This was repeated twice, 2–7 days apart. Flow cytometry assessed total DCs, plasmacytoid DCs, myeloid DCs, total T cells, T helper cells and T cytotoxic cells. No significant trial or interaction effects were found for any variable. A significant main effect of time for all variables was found; immune cells increased from pre‐ to post‐exercise and decreased to baseline 30 min post‐exercise, apart from plasmacytoid DCs, which remained elevated 30 min post‐exercise. Intraclass correlation coefficients showed overall good‐to‐excellent reliability for all immune cells, with smallest real difference and Bland–Altman analysis verifying high reproducibility between trials. These results suggest that the 20/50 exercise test induces reproducible DC and T cell count changes, which, implemented before and after a period of intensified training, may highlight the negative states of overtraining.
Myocardial steatosis across the spectrum of human health and disease
Authors: Oneglia Andrew P. , Szczepaniak Lidia S. , Zaha Vlad G. , Nelson Michael D.
Published: December 2023

Preclinical data strongly suggest that myocardial steatosis leads to adverse cardiac remodelling and left ventricular dysfunction. Using 1H cardiac magnetic resonance spectroscopy, similar observations have been made across the spectrum of health and disease. The purpose of this brief review is to summarize these recent observations. We provide a brief overview of the determinants of myocardial triglyceride accumulation, summarize the current evidence that myocardial steatosis contributes to cardiac dysfunction, and identify opportunities for further research.
The neural control of movement: a century of in vivo motor unit recordings is the legacy of Adrian and Bronk
Authors: Farina Dario , Gandevia Simon
Published: December 2023

In two papers dated 1928 to 1929 in The Journal of Physiology, Edgar Adrian and Detlev Bronk described recordings from motor nerve and muscle fibres. The recordings from motor nerve fibres required progressive dissection of the nerve until a few fibres remained, from which isolated single fibre activity could be detected. The muscle fibre recordings were performed in humans during voluntary contractions with an intramuscular electrode – the concentric needle electrode – that they describe for the first time in the second paper. They recognised that muscle fibres would respond to each impulse sent by the innervating motor neurone and that therefore muscle fibre recordings provided information on the times of activation of the motor nerve fibres which were as accurate as a direct record from the nerve. These observations and the description of the concentric needle electrode opened the era of motor unit recordings in humans, which have continued for almost a century and have provided a comprehensive view of the neural control of movement at the motor unit level. Despite important advances in technology, many of the principles of motor unit behaviour that would be investigated in the subsequent decades were canvassed in the two papers by Adrian and Bronk. For example, they described the concomitant motor neurones’ recruitment and rate coding for force modulation, synchronisation of motor unit discharges, and the dependence of discharge rate on motor unit recruitment threshold. Here, we summarise their observations and discuss the impact of their work. We highlight the advent of the concentric needle, and its subsequent influence on motor control research.

image
Mechanical and tribological properties of diamondlike carbon-coated polycarbonate
Authors: Grenadyorov Alexander S. , Yuriev Yuriy N. , Solovyev Аndrey А. , Runts Artem A. , Oskomov Konstantin V. , Semenov Vyacheslav A. , Sypchenko Vladimir S.
Published: December 2023

To improve the mechanical and tribological properties of polycarbonate, diamondlike carbon (DLC) coating was deposited on its surface by pulsed vacuum arc deposition with different pulse repetition rates at low substrate temperature (not more than 80 °C). The surface hardness increased by 20–33 times, the plasticity index increased by 1.6–2.5 times, the resistance to plastic deformation increased by 50–200 times, and the wear rate decreased by 170–600 times compared to untreated polycarbonate depending on the pulse frequency in the process of coating deposition. It has been shown that decreasing the pulse frequency during DLC deposition from 3 to 1 Hz increases the content of sp3-hybridized carbon atoms and level of internal stresses in the coating and increases its hardness. However, this is accompanied by an increase in the number of microcracks in the coating. Deposition with an optimal pulse frequency formed a polycarbonate/DLC system with high hardness and wear resistance as well as a low number of microcracks.
Organizational-Level Factors That Influence Women Coaches’ Experiences
Authors: Strode James P. , Parker Heidi M. , Kerwin Shannon
Published: December 2023

The purpose of this study was to identify the supports and barriers women coaches experience at the organizational level and to determine how those factors influence interpersonal- and individual-level factors within their coaching context. Nine women who coach high school basketball were interviewed at two time points and asked to reflect on organizational-level factors relative to their coaching position and how those factors have shaped their coaching experience over time. Based on the results of the interviews, two organizational-level factors were identified as barriers for participants: navigating inconsistent hiring practices and hypermasculine culture within school sport. The participants described organizational-level factors as influencing their experiences at both interpersonal (e.g., support from mentors, barriers related to the athletic directors) and individual (e.g., age, experience, sexual orientation) levels. The findings provide empirical support for specific organizational factors that contribute to interpersonal- and individual-level coach experiences. The power structures embedded in these associations are defined and discussed.
Time-resolved serial crystallography to track the dynamics of carbon monoxide in the active site of cytochrome
c
oxidase
Authors: Safari Cecilia , Ghosh Swagatha , Andersson Rebecka , Johannesson Jonatan , Båth Petra , Uwangue Owens , Dahl Peter , Zoric Doris , Sandelin Emil , Vallejos Adams , Nango Eriko , Tanaka Rie , Bosman Robert , Börjesson Per , Dunevall Elin , Hammarin Greger , Ortolani Giorgia , Panman Matthijs , Tanaka Tomoyuki , Yamashita Ayumi , Arima Toshi , Sugahara Michihiro , Suzuki Mamoru , Masuda Tetsuya , Takeda Hanae , Yamagiwa Raika , Oda Kazumasa , Fukuda Masahiro , Tosha Takehiko , Naitow Hisashi , Owada Shigeki , Tono Kensuke , Nureki Osamu , Iwata So , Neutze Richard , Brändén Gisela
Published: December 2023

Cytochrome
c
oxidase (C
c
O) is part of the respiratory chain and contributes to the electrochemical membrane gradient in mitochondria as well as in many bacteria, as it uses the energy released in the reduction of oxygen to pump protons across an energy-transducing biological membrane. Here, we use time-resolved serial femtosecond crystallography to study the structural response of the active site upon flash photolysis of carbon monoxide (CO) from the reduced heme

a
3

of

ba
3

-type C
c
O. In contrast with the

aa
3

-type enzyme, our data show how CO is stabilized on Cu
B
through interactions with a transiently ordered water molecule. These results offer a structural explanation for the extended lifetime of the Cu
B
-CO complex in

ba
3

-type C
c
O and, by extension, the extremely high oxygen affinity of the enzyme.
Estimating birthweight reduction attributable to maternal ozone exposure in low- and middle-income countries
Authors: Tong Mingkun , Xu Huiyu , Wang Ruohan , Liu Hengyi , Li Jiajianghui , Li Pengfei , Qiu Xinghua , Gong Jicheng , Shang Jing , Zhu Tong , Xue Tao
Published: December 2023

The effect of O
3
on birthweight in low- and middle-income countries (LMICs) remains unknown. A multicenter epidemiological study was conducted to evaluate the association between maternal peak-season O
3
exposure and birthweight, using 697,148 singleton newborns obtained in 54 LMICs between 2003 and 2019. We estimated the birthweight reduction attributable to peak-season O
3
exposure in 123 LMICs based on a nonlinear exposure-response function (ERF). With every 10–part per billion increment in O
3
concentration, we found a reduction in birthweight of 19.9 g [95% confidence interval (CI): 14.8 to 24.9 g]. The nonlinear ERF had a monotonic decreasing curve, and no safe O
3
exposure threshold was identified. The mean reduction in birthweight reduction attributable to O
3
across the 123 LMICs was 43.8 g (95% CI: 30.5 to 54.3 g) in 2019. The reduction in O
3
-related birthweight was greatest in countries in South Asia, the Middle East, and North Africa. Effective O
3
pollution control policies have the potential to substantially improve infant health.
Efficient current-induced spin torques and field-free magnetization switching in a room-temperature van der Waals magnet
Authors: Yun Chao , Guo Haoran , Lin Zhongchong , Peng Licong , Liang Zhongyu , Meng Miao , Zhang Biao , Zhao Zijing , Wang Leran , Ma Yifei , Liu Yajing , Li Weiwei , Ning Shuai , Hou Yanglong , Yang Jinbo , Luo Zhaochu
Published: December 2023

The discovery of magnetism in van der Waals (vdW) materials has established unique building blocks for the research of emergent spintronic phenomena. In particular, owing to their intrinsically clean surface without dangling bonds, the vdW magnets hold the potential to construct a superior interface that allows for efficient electrical manipulation of magnetism. Despite several attempts in this direction, it usually requires a cryogenic condition and the assistance of external magnetic fields, which is detrimental to the real application. Here, we fabricate heterostructures based on Fe3GaTe2flakes that have room-temperature ferromagnetism with excellent perpendicular magnetic anisotropy. The current-driven nonreciprocal modulation of coercive fields reveals a high spin-torque efficiency in the Fe3GaTe2/Pt heterostructures, which further leads to a full magnetization switching by current. Moreover, we demonstrate the field-free magnetization switching resulting from out-of-plane polarized spin currents by asymmetric geometry design. Our work could expedite the development of efficient vdW spintronic logic, memory, and neuromorphic computing devices.
Eukaryotic Kv channel Shaker inactivates through selectivity filter dilation rather than collapse
Authors: Stix Robyn , Tan Xiao-Feng , Bae Chanhyung , Fernández-Mariño Ana I. , Swartz Kenton J. , Faraldo-Gómez José D.
Published: December 2023

Eukaryotic voltage-gated K
+
channels have been extensively studied, but the structural bases for some of their most salient functional features remain to be established. C-type inactivation, for example, is an auto-inhibitory mechanism that confers temporal resolution to their signal-firing activity. In a recent breakthrough, studies of a mutant of Shaker that is prone to inactivate indicated that this process entails a dilation of the selectivity filter, the narrowest part of the ion conduction pathway. Here, we report an atomic-resolution cryo–electron microscopy structure that demonstrates that the wild-type channel can also adopt this dilated state. All-atom simulations corroborate this conformation is congruent with the electrophysiological characteristics of the C-type inactivated state, namely, residual K
+
conductance and altered ion specificity, and help rationalize why inactivation is accelerated or impeded by certain mutations. In summary, this study establishes the molecular basis for an important self-regulatory mechanism in eukaryotic K
+
channels, laying a solid foundation for further studies.
Structural basis for subversion of host cell actin cytoskeleton during
Salmonella
infection
Authors: Yuan Biao , Scholz Jonas , Wald Jiri , Thuenauer Roland , Hennell James Rory , Ellenberg Irina , Windhorst Sabine , Faix Jan , Marlovits Thomas C.
Published: December 2023

Secreted bacterial type III secretion system (T3SS) proteins are essential for successful infection by many human pathogens. Both T3SS translocator SipC and effector SipA are critical for
Salmonella
infection by subversion of the host cell cytoskeleton, but the precise molecular interplay between them remains unknown. Here, using cryo–electron microscopy, we show that SipA binds along the F-actin grooves with a unique binding pattern. SipA stabilizes F-actin through charged interface residues and appears to prevent inorganic phosphate release through closure of the “back door” of adenosine 5′-triphosphate pocket. We also show that SipC enhances the binding of SipA to F-actin, thus demonstrating that a sequential presence of T3SS proteins in host cells is associated with a sequence of infection events—starting with actin nucleation, filament growth, and stabilization. Together, our data explain the coordinated interplay of a precisely tuned and highly effective mechanism during
Salmonella
infection and provide a blueprint for interfering with
Salmonella
effectors acting on actin.
Silicon–van der Waals heterointegration for CMOS-compatible logic-in-memory design
Authors: Lee Mu-Pai , Gao Caifang , Tsai Meng-Yu , Lin Che-Yi , Yang Feng-Shou , Sung Hsin-Ya , Zhang Chi , Li Wenwu , Li Jun , Zhang Jianhua , Watanabe Kenji , Taniguchi Takashi , Ueno Keiji , Tsukagoshi Kazuhito , Ho Ching-Hwa , Chu Junhao , Chiu Po-Wen , Li Mengjiao , Wu Wen-Wei , Lin Yen-Fu
Published: December 2023

Silicon CMOS-based computing-in-memory encounters design and power challenges, especially in logic-in-memory scenarios requiring nonvolatility and reconfigurability. Here, we report a universal design for nonvolatile reconfigurable devices featuring a 2D/3D heterointegrated configuration. By leveraging the photo-controlled charge trapping/detrapping process and the partially top-gated energy band landscape, the van der Waals heterostacking achieves polarity storage and logic reconfigurable characteristics, respectively. Precise polarity tunability, logic nonvolatility, robustness against high temperature (at 85°C), and near-ideal subthreshold swing (80 mV dec
−1
) can be done. A comprehensive investigation of dynamic charge fluctuations provides a holistic understanding of the origins of nonvolatile reconfigurability (a trap level of 10
13
cm
−2
eV
−1
). Furthermore, we cascade such nonvolatile reconfigurable units into a monolithic circuit layer to demonstrate logic-in-memory computing possibilities, such as high-gain (65 at
V
dd
= 0.5 V) logic gates. This work provides an innovative 3D heterointegration prototype for future computing-in-memory hardware.
SARS-CoV-2 vaccination enhances the effector qualities of spike-specific T cells induced by COVID-19
Authors: Cai Curtis , Gao Yu , Adamo Sarah , Rivera-Ballesteros Olga , Hansson Lotta , Österborg Anders , Bergman Peter , Sandberg Johan K. , Ljunggren Hans-Gustaf , Björkström Niklas K. , Strålin Kristoffer , Llewellyn-Lacey Sian , Price David A. , Qin Chuan , Grifoni Alba , Weiskopf Daniela , Wherry E. John , Sette Alessandro , Aleman Soo , Buggert Marcus
Published: December 2023

T cells are critical for immune protection against severe COVID-19, but it has remained unclear whether repeated exposure to SARS-CoV-2 antigens delivered in the context of vaccination fuels T cell exhaustion or reshapes T cell functionality. Here, we sampled convalescent donors with a history of mild or severe COVID-19 before and after SARS-CoV-2 vaccination to profile the functional spectrum of hybrid T cell immunity. Using combined single-cell technologies and high-dimensional flow cytometry, we found that the frequencies and functional capabilities of spike-specific CD4
+
and CD8
+
T cells in previously infected individuals were enhanced by vaccination, despite concomitant increases in the expression of inhibitory receptors such as PD-1 and TIM3. In contrast, CD4
+
and CD8
+
T cells targeting non-spike proteins remained functionally static and waned over time, and only minimal effects were observed in healthy vaccinated donors experiencing breakthrough infections with SARS-CoV-2. Moreover, hybrid immunity was characterized by elevated expression of IFN-γ, which was linked with clonotype specificity in the CD8
+
T cell lineage. Collectively, these findings identify a molecular hallmark of hybrid immunity and suggest that vaccination after infection is associated with cumulative immunological benefits over time, potentially conferring enhanced protection against subsequent episodes of COVID-19.
Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis
Authors: Jost Stephanie , Lucar Olivier , Lee Esther , Yoder Taylor , Kroll Kyle , Sugawara Sho , Smith Scott , Jones Rhianna , Tweet George , Werner Alexandra , Tomezsko Phillip J. , Dugan Haley L. , Ghofrani Joshua , Rascle Philippe , Altfeld Marcus , Müller-Trutwin Michaela , Goepfert Paul , Reeves R. Keith
Published: December 2023

Multiple studies have broadened the roles of natural killer (NK) cells functioning as purely innate lymphocytes by demonstrating that they are capable of putative antigen-specific immunological memory against multiple infectious agents including HIV-1 and influenza. However, the mechanisms underlying antigen specificity remain unknown. Here, we demonstrate that antigen-specific human NK cell memory develops upon exposure to both HIV and influenza, unified by a conserved and epitope-specific targetable mechanism largely dependent on the activating CD94/NKG2C receptor and its ligand HLA-E. We validated the permanent acquisition of antigen specificity by individual memory NK cells by single-cell cloning. We identified elevated expression of KLRG1, α4β7, and NKG2C as biomarkers of antigen-specific NK cell memory through complex immunophenotyping. Last, we uncovered individual HLA-E–restricted peptides that may constitute the dominant NK cell response in HIV-1– and influenza-infected persons in vivo. Our findings clarify the mechanisms contributing to antigen-specific memory NK cell responses and suggest that they could be potentially targeted therapeutically for vaccines or other therapeutic interventions.
Anti-
Leishmania
compounds can be screened using
Leishmania
spp. expressing red fluorescence (
tdTomato
)
Authors: Cruz Mariza Gabriela Faleiro de Moura Lodi , Santi Ana Maria Murta , Morais-Teixeira Eliane de , Caldeira Alisson Samuel Portes , Siqueira Ezequias Pessoa de , Oliveira Edward , Alves Tânia Maria de Almeida , Murta Silvane Maria Fonseca
Published: December 2023

The main challenges associated with leishmaniasis chemotherapy are drug toxicity, the possible emergence of resistant parasites, and a limited choice of therapeutic agents. Therefore, new drugs and assays to screen and detect novel active compounds against leishmaniasis are urgently needed. We thus validated
Leishmania braziliensis
(Lb) and
Leishmania infantum
(Li) that constitutively express the tandem tomato red fluorescent protein (
tdTomato
) as a model for large-scale screens of anti-
Leishmania
compounds. Confocal microscopy of
Lb
and
Li::tdTomato
revealed red fluorescence distributed throughout the entire parasite, including the flagellum, and flow cytometry confirmed that the parasites emitted intense fluorescence. We evaluated the infectivity of cloned promastigotes and amastigotes constitutively expressing
tdTomato
, their growth profiles in THP-1 macrophages, and susceptibility to trivalent antimony, amphotericin, and miltefosine
in vitro
. The phenotypes of mutant and wild-type parasites were similar, indicating that the constitutive expression of
tdTomato
did not interfere with the evaluated parameters. We applied our validated model to a repositioning strategy and assessed the susceptibility of the parasites to eight commercially available drugs. We also screened 32 natural plant and fungal extracts and 10 pure substances to reveal new active compounds. The infectivity and Glucantime treatment efficacy of BALB/c mice and golden hamsters infected with
Lb
and
Li::tdTomato
mutant lines, respectively, were very similar compared to animals infected with wild-type parasites. Standardizing our methodology would offer more rapid, less expensive, and easier assays to screen of compounds against
L. braziliensis
and
L. infantum in vitro
and
in vivo
. Our method could also enhance the discovery of active compounds for treating leishmaniasis.
Whole-genome sequence of
Geobacillus thermodenitrificans
K1041, a genetically tractable strain representative of the genus
Geobacillus
Authors: Kani Saori , Suzuki Hirokazu
Published: December 2023

We present the whole-genome sequence of
Geobacillus thermodenitrificans
K1041, a bacterium that was originally identified as a genetically tractable thermophile. The genome consists of a circular chromosome that contains 3,848 genes. The sequence has a total size of 3,755,826 bp with a GC content of 49.18%.
Complete genome sequences and characteristics of mycobacteriophages Diminimus, Dulcita, Glaske16, and Koreni
Authors: Baliraine Faith W. , Mathews Kaitlyn E. , Livingston Emma G. , Martinez Clarissa A. , Donnelly Olivia L. , Pledger Taryn M. , Feroz Tadeen , Harbison Zoe J. , Schlimme Sarah G. , Andrade Camila , Salazar Keren N. , Berryhill Elise C. , DeLosSantos Madelyn M. , Foree Hannah L. , Gicheru Wanjiru , Jett Adrienne M. , Mendez Sofia N. , Odebiyi Toluwalope M. , Pitman Jacob I. , Tan Michael J. , McLoud Josh D. , Baliraine Frederick N.
Published: December 2023

Complete genome sequences of four novel mycobacteriophages, Diminimus, Dulcita, Glaske16, and Koreni, isolated from soil are presented. All these bacteriophages belong to subcluster M1, except Koreni that belongs to subcluster A4. Moreover, all have siphovirus morphologies, with genome sizes ranging from 51,055 to 81,156 bp.
Integrase-associated niche differentiation of endogenous large DNA viruses in crustaceans
Authors: Kawato Satoshi , Nozaki Reiko , Kondo Hidehiro , Hirono Ikuo
Published: December 2023

Crustacean genomes harbor sequences originating from nimaviruses, a family of large double-stranded DNA viruses infecting crustaceans. In this study, we recovered metagenome-assembled genomes of 27 endogenous nimaviruses from crustacean genome data. Phylogenetic analysis revealed four major lineages within
Nimaviridae
, and for three of these lineages, we propose novel genera of endogenous nimaviruses: “Majanivirus” and “Pemonivirus” identified from penaeid shrimp genomes, and “Clopovirus” identified from terrestrial isopods. Majanivirus genomes contain multiple eukaryotic-like genes such as baculoviral inhibitor of apoptosis repeat-containing genes, innexins, and heat shock protein 70-like genes, some of which contain introns. An alignment of long reads revealed that each endogenous nimavirus species specifically inserts into host microsatellites or within 28S rDNA. This insertion preference was associated with the type of virus-encoded DNA recombination enzymes, the integrases. Majaniviruses, pemoniviruses, some whispoviruses, and possibly clopoviruses specifically insert into the arthropod telomere repeat motif (TAACC/GGTTA)n and all possessed a specific tyrosine recombinase family. Pasiphaea japonica whispovirus and Portunus trituberculatus whispovirus, the closest relatives of white spot syndrome virus, integrate into the host 28S rDNA and are equipped with members of another family of tyrosine recombinases that are distantly related to telomere-specific tyrosine recombinases. Endogenous nimavirus genomes identified from sesarmid crabs, which lack tyrosine recombinases and are flanked by a 46-bp inverted terminal repeat, integrate into (AT/TA)n microsatellites through the acquisition of a Ginger2-like cut-and-paste DDE transposase. These results suggest that endogenous nimaviruses are giant transposable elements that occupy different sequence niches through the acquisition of different integrase families.

IMPORTANCE

Crustacean genomes harbor sequences originating from a family of large DNA viruses called nimaviruses, but it is unclear why they are present. We show that endogenous nimaviruses selectively insert into repetitive sequences within the host genome, and this insertion specificity was correlated with different types of integrases, which are DNA recombination enzymes encoded by the nimaviruses themselves. This suggests that endogenous nimaviruses have colonized various genomic niches through the acquisition of integrases with different insertion specificities. Our results point to a novel survival strategy of endogenous large DNA viruses colonizing the host genomes. These findings may clarify the evolution and spread of nimaviruses in crustaceans and lead to measures to control and prevent the spread of pathogenic nimaviruses in aquaculture settings.
Quantitative assessment of multiple pathogen exposure and immune dynamics at scale
Authors: Song Lusheng , Rauf Femina , Hou Ching-Wen , Qiu Ji , Murugan Vel , Chung Yunro , Lai Huafang , Adam Deborah , Magee D. Mitchell , Trivino Soto Guillermo , Peterson Milene , Anderson Karen S. , Rice Stephen G. , Readhead Benjamin , Park Jin G. , LaBaer Joshua
Published: December 2023

Serological responses reveal recent and historical exposure to pathogens, as well as the state of autoimmune and other chronic conditions, including cancer. Serological tests either assess one or a few antigens in many people, or multiple antigens for modest sample sizes. Here, we describe a multiplexed serology method that evaluates samples at the scale of thousands. This molecular epidemiology tool operates at a population scale sufficient to evaluate broadly how various infectious exposures or autoimmune responses affect health. The method employs full-length folded proteins, is quantitative over a wide dynamic range, and performs favorably compared with commercial clinical assays [severe acute respiratory syndrome coronavirus 2 chemiluminescent IgG II assay (Beckman) and Platelia SARS-CoV-2 total Ab enzyme-linked immunosorbent assay (Bio-Rad, California, USA)]. Responses to 39 bacteria species/strains and 99 viruses in 2,400 people were evaluated. Subjects with longitudinal data showed quantitative stability of response to all antigens over the 6-month time window, enabling the detection of intervening clinical events. We expect this highly adaptable method will find broad application in immune profile tracking.

IMPORTANCE

Serology reveals exposure to pathogens, as well as the state of autoimmune and other clinical conditions. It is used to evaluate individuals and their histories and as a public health tool to track epidemics. Employing a variety of formats, studies nearly always perform serology by testing response to only one or a few antigens. However, clinical outcomes of new infections also depend on which previous infections may have occurred. We developed a high-throughput serology method that evaluates responses to hundreds of antigens simultaneously. It can be used to evaluate thousands of samples at a time and provide a quantitative readout. This tool will enable doctors to monitor which pathogens an individual has been exposed to and how that changes in the future. Moreover, public health officials could track populations and look for infectious trends among large populations. Testing many potential antigens at a time may also aid in vaccine development.