bluuebunny/crossref_metadata_2025 huggingface dataset:
Combiningin vivoandin vitroapproaches to better understand host-pathogen interactions
Authors: Holdbrook Robert , Reavey Catherine E. , Randall Joanna L. , Andongma Awawing A. , Tummala Yamini , Simpson Stephen J. , Smith Judith A. , Cotter Sheena C. , Wilson Kenneth
Published: April 2024

Nutrition often shapes the outcome of host-parasite interactions, however understanding the mechanisms by which this occurs is confounded by the intimate nature of the association and by the fact that the host and parasite may compete for the same limiting nutrients. One way of disentangling this interaction is to combinein vivoandin vitroapproaches. Here, we explore the role of host nutrition in determining the outcome of infections using a model insect-bacterium system: the cotton leafwormSpodoptera littoralisand the blood-borne bacteriumXenorhabdus nematophila.

Spodoptera littoralislarvae were reared on one of a series of 20 chemically-defined diets ranging in their protein: carbohydrate (P:C) ratio and caloric density. They were then challenged with either a fixed dose ofX. nematophilacells (live or dead) or were sham-injected. Survivorship of larvae challenged with live bacterial cells was strongly dependent on the protein levels of the diet, with mortality being highest on low-protein diets. This trend was reflected in the bacterial growth ratein vivo, which peaked in larvae fed low-protein diets.

To determine whetherin vivobacterial growth rates were driven by blood nutrients, rather than an enhanced host immune response, we generated 20 synthetic haemolymphs (‘nutribloods’) that mimicked the nutritional content of host blood. Bacterial growth rate in the nutribloods was also negatively impacted by their protein content suggesting that nutrient availability and not host immunity was driving the interaction. By comparing standardized bacterial growth ratesin vivoandin vitro, we conclude that the outcome of this host-parasite interaction is largely driven by ‘bottom-up’ effects of nutrients on bacterial growth, rather than by ‘top-down’ effects of nutrients on host-mediated immune responses. The outcome of host-parasite interactions is typically assumed to be strongly determined by the host immune response. The direct effects of nutrition have been underexplored and may have broad consequences for host-parasite interactions across taxa.
Site-Specific Investigation of DNA Holliday Junction Dynamics and Structure with 6-Methylisoxanthopterin, a Fluorescent Guanine Analog
Authors: Lombardo Zane , Mukerji Ishita
Published: April 2024

DNA Holliday Junction (HJ) formation and resolution is requisite for maintaining genomic stability in processes such as replication fork reversal and double-strand break repair. If HJs are not resolved, chromosome disjunction and aneuploidy result, hallmarks of tumor cells. To understand the structural features that lead to processing of these four-stranded joint molecule structures, we seek to identify structural and dynamic features unique to the central junction core. We incorporate the fluorescent guanine analog 6-methylisoxanthopterin (6-MI) at ten different locations throughout a model HJ structure to obtain site-specific information regarding the structure and dynamics of bases relative to those in a comparable sequence context in duplex DNA. These comparisons were accomplished through measuring fluorescence lifetime, relative brightness, fluorescence anisotropy, and thermodynamic stability, along with fluorescence quenching assays. These time-resolved and steady-state fluorescence measurements demonstrate that the structural distortions imposed by strand crossing result in increased solvent exposure, less stacking of bases and greater extrahelical nature of bases within the junction core. The 6-MI base analogs in the junction reflect these structural changes through an increase in intensity relative to those in the duplex. Molecular dynamics simulations performed using a model HJ indicate the primary sources of deformation are in the shift and twist parameters of the bases at the central junction step. These results suggest that junction-binding proteins may use the unique structure and dynamics of the bases at the core for recognition.
Enhancing Agrobacterium-Mediated Soybean Transformation Efficiency with an Auxiliary Solution
Authors: Chen Luying , Wang Liang , Li Yongguang , Han Shaojie
Published: April 2024

Soybean provides oil, protein, and biofuel. Efficient transformation systems are vital for advancing soybean research. Currently,Agrobacterium rhizogenes-mediated transformation is the predominant method for facilitating rapid transformation, producing transgenic hairy roots. However, the limitations of soybean transformation technology primarily originate from its low efficiency and genotype dependency, leaving significant room for improvement in the development more universally applicable and efficient methods. In this study, we explored the enhancement of soybean transformation efficiency through the generation and validation of three reporter vectors (ZsGreen, TdTomato, and Ruby) and the strategic use ofAgrobacteriumAuxiliary Solution (AAS) containing Silwet L-77 and hormone mixtures. Our findings demonstate that the incorporation of hormone mixtures and Silwet L-77 into AAS significantly improves hairy root transformation rates. Specifically, the combination of hormone mixtures with Silwet L-77 substantially increased both total root and cotyledon transformation efficiencies compared to the control. We also assessed the impact of vector size on transformation efficiency, observing a notable decrease in efficiency with larger vectors such as the Ruby cassette compared to smaller markers like GFP and RFP. Furthermore, our study examined the effects of AAS on the co-transformation rate of two separate vectors, revealing a slight but significant reduction in efficiency compared to single vector transformations. Additionally, we evaluated the role of AAS in enhancing soybean hypocotyl transformation rates in composite soybean plants across various varieties. The results consistently showed an increase in both positive roots and explant efficiencies with the addition of AAS, indicating its broad applicability and effectiveness in soybean transformation. However, significant varietal differences in transformation rates were observed, particularly between “Forrest” and other varieties such as “Williams 82” and “Dongnong 50”. In summary, our research emphasizes the significant role of auxiliary agents and vector size in optimizing soybean transformation techniques, providing valuable insights for future advancements in soybean genetic modification and biotechnological research.
Single Channel Electrocardiography Optimizes the Diagnostic Accuracy of Bicycle Ergometry
Authors: Marzoog Basheer Abdullah , Abdullaev Magomed , Suvorov Alexander , Chomakhidze Peter , Gognieva Daria , Gagarina Nina Vladimirovna , Mozzhukhina Natalia , Kostin Sergey Vladimirovich , Bestavashvili Afina Aftandilovna , Fominykha Ekaterina , Kopylov Philipp
Published: April 2024

Background

Ischemic heart disease (IHD) has the highest mortality rate in the globe. This returns to the poor diagnostic and therapeutic strategies including the early prevention methods.

Aims

To assess the changes in the single channel electrocardiography (SCECG) at rest and on exercise test in patients with vs without IHD confirmed by stress computed tomography myocardial perfusion (CTP) imaging with vasodilatation stress-test.

Objectives

IHD frequently have preventable risk factors and causes that lead to the disease appearance. However, the lack of the proper diagnostic and prevention tools remains a global challenge in or era despite the current scientific advances.

Material and methods

A single center observational study included 38 participants from Moscow. The participants aged ≥ 40 years and given a written consent to participate in the study. Both groups, G1=19 with vs G2=19 without post stress induced myocardial perfusion defect, passed consultation by cardiologist, anthropometric measurements, blood pressure and pulse rate, echocardiography, cardio-ankle vascular index, performing bicycle ergometry, recording 3-minutes SCECG (using CARDO-QVARK ) before and just after bicycle ergometry, and then performing CTP. The LASSO regression with nested cross-validation was used to find association between CARDO-QVARK parameters and the existence of the perfusion defect. Statistical processing carried out using the R programming language v4.2 and Python v.3.10 [^R].

Results

The CARDO-QVARK parameters analysis have a specificity 63.2 % [95 % confidence interval (CI); 0.391 ; 0.833], sensitivity 73.7 % [95 % CI ; 0.533 ; 0.929], area under the curve (AUC) 68.4 % [95 % CI ; 0.527 ; 0.817] in compare to bicycle ergometry (AUC; 55.3 %), based on our study results.

Conclusion

The SCECG have significantly higher diagnostic accuracy in compare to bicycle ergometry. CARDO-QVARK has the potential to improve the diagnostic accuracy of the bicycle ergometry.

Other

Further investigations required to uncover the hidden capabilities of CARDO-QVARK in the diagnosis of ischemic heart disease.
The potential impact of the spreading of highly transmissible Omicron variant XBB.1.5 and JN.1 on the evolution of SARS-CoV-2
Authors: Yi Buqing
Published: April 2024

In spite of three-year pandemic time caused by Covid-19, the trend and impact of the evolution of SARS-CoV-2 remain unclear. For newly emerging variants, it is still hard to predict how possibly they could impact the pandemic/endemic course. The spreading of the highly transmissible variant XBB.1.5 and JN.1 has brought many questions. Could the high transmission ability of such variant lead to a different global spreading pattern compared to other previously existing variants of concern (VOCs)? How that may possibly affect the further evolution of SARS-CoV-2? This study aimed to explore the evolution course of SARS-CoV-2 variants, with focus on VOCs. The investigation was carried out through integration of multiple virus genomic epidemiology approaches. Phylogeny and phylodynamic analyses were used to investigate dynamic changes of virus evolution course. Through this study, an overview check of the evolution events of SARS-CoV-2 VOCs, including the alpha variant, delta variant and omicron variant, has been performed, and the further course of evolution has been predicted, especially taking the potential impact of the spreading of XBB.1.5 and JN.1 into consideration. Furthermore, the early spreading pattern of XBB.1.5 was compared with the early spreading patterns of BQ.1.1 to investigate the impact of evolution on virus spreading pattern. The information acquired through this study provided insights into the effect of SARS-CoV-2 evolution on spreading pattern and the potential impact of the spreading of XBB.1.5 and JN.1 on the further evolution of SARS-CoV-2.
Binette: a fast and accurate bin refinement tool to construct high quality Metagenome Assembled Genomes
Authors: Mainguy Jean , Hoede Claire
Published: April 2024

Metagenomics enables the study of microbial communities and their individual members through shotgun sequencing. An essential phase of metagenomic analysis is the recovery of metagenome-assembled genomes (MAGs). In a metagenomic analysis, sequence reads are assembled into contigs, which are then grouped into bins based on common characteristics - a process known as binning - to generate MAGs. The approach of applying multiple binning methods and combining them in a process called bin refinement allows us to obtain more and higher quality MAGs from metagenomic datasets. We present Binette, a bin refinement tool inspired by metaWRAP’s bin refinement module, which addresses the limitations of the latter and ensures better results. Binette achieves this by creating new hybrid bins using basic set operations from the input bin sets. CheckM2 is then used to assess bin quality and select the best possible bins.
Characterization of the novelSmsHSP24.1Promoter: Unveiling its abiotic stress-inducible expression in transgenic Eggplant (Solanum melongenaL.)
Authors: Khatun Mst. Muslima , Khan Imran , Borphukan Bhabesh , Das Keshob Chandra , Khan Haseena , Islam Mohammad Riazul , Reddy Malireddy K , Salimullah Md
Published: April 2024

Promoters play a pivotal role in regulating gene expression, orchestrating vital processes in plants, including their responses to various environmental stresses. In this study, we focus on the comprehensive characterization of theSmsHSP24.1promoter, a novelcis-acting element, within the context of transgenic Eggplant (Solanum melongenaL.). This detailed analysis shed light on the intricate mechanisms governingSmsHSP24.1promoter-driven gene regulation, particularly in response to adverse environmental challenges such as heat, salt and drought stressors offering valuable insights into its role in plant stress adaptation. The advances in our understanding of promoter-driven gene regulation also contribute to the broader goal of enhancing crop resilience to abiotic stresses, positioning theSmsHSP24.1promoter as a promising tool in agricultural biotechnology applications.

Highlights:

Demonstrated that the full-length 2.0 kb SmsHSP24.1 promoter significantly enhances gene expression under heat stress, with an observable decline in expression with promoter truncation.

Identified specific regulatory elements within the SmsHSP24.1 promoter that are decisive for inducible expression in response to abiotic stresses such as heat, salt, and drought.

Highlighted the utility of the SmsHSP24.1 promoter in crop improvement programs, offering a tool for developing transgenic plant tolerance to combined stresses.
Component specific responses of the microbiomes to common chemical stressors in the human food chain
Authors: Wasimuddin  , Chiaia-Hernandez Aurea , Terrettaz Céline , Thoenen Lisa , Caggìa Veronica , Matteo Pierre , Coll-Crespi Miquel , Notter Matheus , Mukherjee Mohana , Chavez-Capilla Teresa , Ronchi Francesca , Ganal-Vonarburg Stephanie C. , Grosjean Martin , Bigalke Moritz , Spielvogel Sandra , Macpherson Andrew , Mestrot Adrien , Hapfelmeier Siegfried , Erb Matthias , Schlaeppi Klaus , Ramette Alban
Published: April 2024

Along a food chain, microbiomes occur in each component and often contribute to the functioning or the health of their host or environment. ‘One Health’ emphasizes the connectivity of each component’s health. Chemical stress typically causes dysbiotic microbiomes, but it remains unclear whether chemical stressors consistently affect the microbiomes along food chain components. Here, we systematically challenged a model food chain, including water, sediments, soil, plants, and animals, with three chemical stresses consisting of arsenic (a toxic trace element), benzoxazinoids (an abundant bioactive plant metabolites), and terbuthylazine (an herbicide typically found along a human food chain). The analysis of 1,064 microbiome profiles for commonalities and differences in their stress responses indicated that chemical stressors decreased microbiome diversity in soil and animal, but not in the other microbiomes. In response to stress, all food chain communities strongly shifted in their composition, generally becoming compositionally more similar to each other. In addition, we observed stochastic effects in host-associated communities (plant, animal). Dysbiotic microbiomes were characterized by different sets of bacteria, which responded specifically to the three chemical stressors. Microbial co-occurrence patterns significantly shifted with either decreased (water, sediment, plant, animal) or increased (soil) network sparsity and numbers of keystone taxa following stress treatments. This suggested major re-distribution of the roles that specific taxa may have, with the community stability of plant and animal microbiomes being the most affected by chemical stresses. Overall, we observed stress- and component-specific responses to chemical stressors in microbiomes along the model food chain, which could have implications on food chain health.
A Blueprint for Broadly Effective Bacteriophage Therapy Against Bacterial Infections
Authors: Kim Minyoung Kevin , Chen Qingquan , Echterhof Arne , McBride Robert C. , Pennetzdorfer Nina , Banaei Niaz , Burgener Elizabeth B. , Milla Carlos E. , Bollyky Paul L.
Published: April 2024

Bacteriophage therapy is a tantalizing therapeutic option for anti-microbial resistant bacterial infections but is currently limited to personalized therapy due to the narrow host range of individual phages. Theoretically, cocktails incorporating numerous phages targeting all possible bacterial receptor specificities could confer broad host range. Practically, however, extensive bacterial diversity and the complexity of phage-phage interactions precludes this approach. Here, using screening protocols for identifying “complementarity groups” of phages using non-redundant receptors, we generate effective, broad-range phage cocktails that prevent emergence of bacterial resistance. Further, phage complementarity groups have characteristic interactions with particular antibiotic classes, making it possible to predict phage-antibiotic as well as phage-phage interactions. Using this strategy, we generate three phage-antibiotic cocktails, each effective against >96% of 153Pseudomonas aeruginosaclinical isolates, including when used in biofilm cultures and wound infectionsin vivo. We similarly develop effectiveStaphylococcus aureusphage-antibiotic cocktails and demonstrate the utility of combined cocktails against polymicrobial (mixedP. aeruginosa/S. aureus) cultures, highlighting the broad applicability of this approach. These studies establish a blueprint for effective, broad-spectrum phage therapy cocktails and enable off-the-shelf phage-based therapeutics for antimicrobial-resistant bacterial infections.
Engineering, structure, and immunogenicity of a Crimean–Congo hemorrhagic fever virus pre-fusion heterotrimeric glycoprotein complex
Authors: McFadden Elizabeth , Monticelli Stephanie R. , Wang Albert , Ramamohan Ajit R. , Batchelor Thomas G. , Kuehne Ana I. , Bakken Russell R. , Tse Alexandra L. , Chandran Kartik , Herbert Andrew S. , McLellan Jason S.
Published: April 2024

Crimean–Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus that can cause severe disease in humans with case fatality rates of 10–40%. Although structures of CCHFV glycoproteins GP38 and Gc have provided insights into viral entry and defined epitopes of neutralizing and protective antibodies, the structure of glycoprotein Gn and its interactions with GP38 and Gc have remained elusive. Here, we used structure-guided protein engineering to produce a stabilized GP38-Gn-Gc heterotrimeric glycoprotein complex (GP38-GnH-DS-Gc). A cryo-EM structure of this complex provides the molecular basis for GP38’s association on the viral surface, reveals the structure of Gn, and demonstrates that GP38-Gn restrains the Gc fusion loops in the prefusion conformation, facilitated by an N-linked glycan attached to Gn. Immunization with GP38-GnH-DS-Gc conferred 40% protection against lethal IbAr10200 challenge in mice. These data define the architecture of a GP38-Gn-Gc protomer and provide a template for structure-guided vaccine antigen development.
How Mycobacterium tuberculosis builds a home: Single-cell analysis reveals M. tuberculosis ESX-1-mediated accumulation of anti-inflammatory macrophages in infected mouse lungs
Authors: Zheng Weihao , Borja Michael , Dorman Leah , Liu Jonathan , Zhou Andy , Seng Amanda , Arjyal Ritwicq , Sunshine Sara , Nalyvayko Alina , Pisco Angela , Rosenberg Oren , Neff Norma , Zha Beth Shoshana
Published: April 2024

Mycobacterium tuberculosis (MTB) infects and replicates in lung mononuclear phagocytes (MNPs) with astounding ability to evade elimination. ESX-1, a type VII secretion system, acts as a virulence determinant that contributes to MTB’s ability to survive within MNPs, but its effect on MNP recruitment and/or differentiation remains unknown. Here, using single-cell RNA sequencing, we studied the role of ESX-1 in MNP heterogeneity and response in mice and murine bone marrow-derived macrophages (BMDM). We found that ESX-1 is required for MTB to recruit diverse MNP subsets with high MTB burden. Further, MTB induces an anti-inflammatory signature in MNPs and BMDM in an ESX-1 dependent manner. Similarly, spatial transcriptomics revealed an upregulation of anti-inflammatory signals in MTB lesions, where monocyte-derived macrophages concentrate near MTB-infected cells. Together, our findings suggest that MTB ESX-1 mediates the recruitment and differentiation of anti-inflammatory MNPs, which MTB can infect and manipulate for survival.
Nanocluster-antibody-drug conjugates (NADC) as an intravesical precision theranostic agent for interstitial cystitis
Authors: Lin Zhijun , Wang Wanyan , Liu Dingxin , Xu Zhifeng , Wu Zhiming , Zhou Xiangfu , Zhang Xiaodong , Huang Yong , Zhao Qi , Yang Jiang
Published: April 2024

Interstitial cystitis (IC) is a chronic inflammatory disorder characterized by recurring severe pain in the bladder and surrounding pelvic areas, lacking timely diagnostic and therapeutic options. Here, we propose a unitary theranostic nanocluster-antibody-drug conjugate (NADC) by covalently placing dihydroorotate dehydrogenase inhibitors (DHODHi) and ultrasmall gold quantum clusters (AuQCs) on a nerve growth factor (NGF) antagonistic antibody with simultaneous X-ray computed tomographic and near-infrared fluorescence imaging contrasts. Combining anti-inflammatory effects from all individual components, intravesical NADC specifically homed to bladder mucosal lesions and capably alleviated inflammation in chronic, acute, and prophylactic IC models of rats, as revealed by behavioral and pathological evaluations. Transcriptomics unveiled cytokine modulation and concomitant inhibition of perturbed IL-17, NF-κB, TNF, and JAK-STAT signaling pathways. Interestingly, the NADC reconstructed the host bladder microbiota by differentially varying anti-inflammatory and pro-inflammatory bacteria diversities. Distinct from conventional nanoparticles conjugated with antibodies and drugs, NADC relies on the antibody framework and represents a state-of-the-art category of precision theranostic agents with translational potential for diagnosing and treating IC patients.
Energetically costly functional network dynamics in cognitively impaired multiple sclerosis patients
Authors: Broeders T.A.A. , van Dam M. , Pontillo G. , Rauh V. , Douw L. , van der Werf Y.D. , Killestein J. , Barkhof F. , Vinkers C.H. , Schoonheim M.M.
Published: April 2024

Background and objectives

Patients with multiple sclerosis (MS) often experience cognitive impairment, and this is related to structural disconnection and subsequent functional reorganization. It is not clear how specific patterns of functional reorganization might make it harder for cognitively impaired (CI) MS patients to dynamically adapt how brain regions communicate, which is crucial for normal cognition. To identify patterns relevant to cognitive impairment in MS, we performed a temporally detailed analysis of connectivity state transitions and quantified the effort associated with such dynamic alterations.

Methods

Resting-state functional and diffusion MRI was acquired from 95 controls and 330 MS patients (mean disease duration: 15 years) in a cross-sectional design, of whom 86 were classified as CI (≥2/7 domains Z < −2) and 65 as mildly CI (≥2/7 domains Z < −1.5) based on the performance on an expanded Brief Repeatable Battery of Neuropsychological Tests. Four functional connectivity states were determined usingK-means clustering of moment-to- moment co-fluctuations (i.e., edge time series), and the resulting state sequence was used to characterize the frequency of transitions between network configurations. The control energy associated with the transitions between states was then calculated using the structural network of each subject with network control theory.

Results

CI patients transition less frequently between connectivity states. Relative to the time spent in a particular state, CI patients specifically transition less from a weakly connected and highly modular state (i.e., theweakly connected state) to a more integrated state that featured strong involvement of the visual network (i.e., thevisual network state), but more in the opposite direction. CI patients also required more control energy to transition between states.

Discussion

This study showed that it became more effortful for MS patients with cognitive impairment to dynamically change the organization of the functional network, providing an intuitive understanding of why these transitions occur less frequently in some patients. In particular, transitions between theweakly connected stateand the more integratedvisual network statewere relevant for cognition in these patients. The findings highlight a possible underpinning of disturbed cognition in MS patients and also provide novel avenues for studying and possibly improving network dynamics.
Age and gender profiles of HIV infection burden and viraemia: novel metrics for HIV epidemic control in African populations with high antiretroviral therapy coverage
Authors: Brizzi Andrea , Kagaayi Joseph , Ssekubugu Robert , Abeler-Dörner Lucie , Blenkinsop Alexandra , Bonsall David , Chang Larry W. , Fraser Christophe , Galiwango Ronald M. , Kigozi Godfrey , Kyle Imogen , Monod Mélodie , Nakigozi Gertrude , Nalugoda Fred , Rosen Joseph G. , Laeyendecker Oliver , Quinn Thomas C. , Grabowski M. Kate , Reynolds Steven J. , Ratmann Oliver
Published: April 2024

Introduction

To prioritize and tailor interventions for ending AIDS by 2030 in Africa, it is important to characterize the population groups in which HIV viraemia is concentrating.

Methods

We analysed HIV testing and viral load data collected between 2013-2019 from the open, population-based Rakai Community Cohort Study (RCCS) in Uganda, to estimate HIV seroprevalence and population viral suppression over time by gender, one-year age bands and residence in inland and fishing communities. All estimates were standardized to the underlying source population using census data. We then assessed 95-95-95 targets in their ability to identify the populations in which viraemia concentrates.

Results

Following the implementation of Universal Test and Treat, the proportion of individuals with viraemia decreased from 4.9% (4.6%-5.3%) in 2013 to 1.9% (1.7%-2.2%) in 2019 in inland communities and from 19.1% (18.0%-20.4%) in 2013 to 4.7% (4.0%-5.5%) in 2019 in fishing communities. Viraemia did not concentrate in the age and gender groups furthest from achieving 95-95-95 targets. Instead, in both inland and fishing communities, women aged 25-29 and men aged 30-34 were the 5-year age groups that contributed most to population-level viraemia in 2019, despite these groups being close to or had already achieved 95-95-95 targets.

Conclusions

The 95-95-95 targets provide a useful benchmark for monitoring progress towards HIV epidemic control, but do not contextualize underlying population structures and so may direct interventions towards groups that represent a marginal fraction of the population with viraemia.
Commensal bacteria inhibit viral infections via a tryptophan metabolite
Authors: Jiang Danting , Soo Nicole , Tan Chin Yee , Dankwa Sedem , Wang Hsuan-Yuan , Theriot Barbara S. , Ardeshir Amir , Siddiqui Nazema Y. , Rompay Koen K. A. Van , Paris Kristina De , Permar Sallie R. , Goswami Ria , Surana Neeraj K.
Published: April 2024

There is growing appreciation that commensal bacteria impact the outcome of viral infections, though the specific bacteria and their underlying mechanisms remain poorly understood. Studying a simian–human immunodeficiency virus (SHIV)-challenged cohort of pediatric nonhuman primates, we bioinformatically associatedLactobacillus gasseriand the bacterial family Lachnospiraceae with enhanced resistance to infection. We experimentally validated these findings by demonstrating two different Lachnospiraceae isolates,Clostridium immunisandRuminococcus gnavus, inhibited HIV replication in vitro and ex vivo. Given the link between tryptophan catabolism and HIV disease severity, we found that an isogenic mutant ofC. immunisthat lacks the aromatic amino acid aminotransferase (ArAT) gene, which is key to metabolizing tryptophan into 3-indolelactic acid (ILA), no longer inhibits HIV infection. Intriguingly, we confirmed that a second commensal bacterium also inhibited HIV in an ArAT-dependent manner, thus establishing the generalizability of this finding. In addition, we found that purified ILA inhibited HIV infection by agonizing the aryl hydrocarbon receptor (AhR). Given that the AhR has been implicated in the control of multiple viral infections, we demonstrated thatC. immunisalso inhibited human cytomegalovirus (HCMV) infection in an ArAT-dependent manner. Importantly, metagenomic analysis of individuals at-risk for HIV revealed that those who ultimately acquired HIV had a lower fecal abundance of the bacterial ArAT gene compared to individuals who did not, which indicates our findings translate to humans. Taken together, our results provide mechanistic insights into how commensal bacteria decrease susceptibility to viral infections. Moreover, we have defined a microbiota-driven antiviral pathway that offers the potential for novel therapeutic strategies targeting a broad spectrum of viral pathogens.
Liming enhances the abundance and stability of nitrogen-cycling microbes: The buffering effect of long-term lime application
Authors: Mitsuta Akari , Lourenco Kesia Silva , Chang Jingjing , Ros Mart , Schils René , Uchida Yoshitaka , Kuramae Eiko Eurya
Published: April 2024

Lime application (liming) has historically been used to ameliorate soil acidity in grasslands. Liming effectively improves soil pH, plant productivity, and soil physicochemical properties, but the long-term impact of acidity control by liming on key microbial nitrogen (N)-cycling genes in semi-natural grasslands is unknown. We investigated the effect of 65 years of liming on N-cycling processes in the limed and control plots of the Ossekampen long-term grassland experiment in the Netherlands. These plots have not received any other fertilizers for 65 years. Soil sampling and nitrous oxide (N2O) emission measurements were conducted three times in spring and four times in summer, and quantitative real-time PCR was performed to determine the abundances of N-cycling genes, including ammonia-oxidation (amoA), denitrification (nirS,nirK,nosZ), and N-fixation (nifH) genes. Long-term liming increased the abundances of nitrifiers and denitrifiers but did not increase N2O emissions. Additionally, liming had a buffering effect that stabilized the population of N-cycling microbes against seasonal variations in abundance. Our results indicate that improving soil acidity through liming facilitates microbial N-cycling processes without increasing N2O emissions.

Highlights:

65 years of liming increased bacterial but not archaeal and fungal community abundance.

Liming increased the abundance of microbial N-cycling genes.

The buffering effect of liming reduced seasonal variations in the abundance of N microbes.
Heteroallelic combination of anillin mutants reveals cytoskeletal uncoupling during cytokinesis.
Authors: Chambaud Guillaume , Carim Sabrya C , Hickson Gilles R X
Published: April 2024

Cytokinetic contractile rings close, disassemble and transition to midbody rings through poorly understood mechanisms. We previously showed that this transition in Drosophila S2 cells requires both Citron kinase (Sticky) and septins, acting on the N- and C-terminus, respectively, of the scaffold protein, Anillin. To better understand the coordination of these proteins, we performed deplete-and-rescue experiments using Anillin mutants defective in Sticky interaction or septin recruitment. Expressing each mutant individually as two copies tagged with GFP and mCherry revealed comparable behaviors of the tags and characteristic cytokinesis failure phenotypes. However, trans-heterozygous combination of both Anillin mutants rescued the cytokinesis defects, with both mutants clearly exhibiting different localization patterns. Thus, the essential N- and C-terminus-mediated roles of Anillin can be satisfied by different molecules of Anillin that cannot bind to Sticky and to septins simultaneously. We conclude that Anillin organizes distinct cytoskeletal elements that are uncoupled from one another and that their physical separation drives the transition from contractile ring to midbody ring.
The role of chloroplast SRP54 domains and its C-terminal tail region in post- and cotranslational protein transportin vivo
Authors: Bischoff Annika , Ortelt Jennifer , Dünschede Beatrix , Zegarra Victor , Bedrunka Patricia , Bange Gert , Schünemann Danja
Published: April 2024

In the chloroplast, the 54 kDa subunit of the signal recognition particle (cpSRP54) is involved in the posttranslational transport of the light-harvesting chlorophyll a/b-binding proteins (LHCPs) and the cotranslational transport of plastid-encoded subunits of the photosynthetic complexes to the thylakoid membrane. It forms a high-affinity complex with plastid-specific cpSRP43 for posttranslational transport, while a ribosome-associated pool coordinates its cotranslational function. CpSRP54 constitutes a conserved multidomain protein, comprising a GTPase (NG) and a methionine-rich (M) domain linked by a flexible region. It is further characterized by a plastid-specific C-terminal tail region containing the cpSRP43-binding motif. To characterize the physiological role of the various regions of cpSRP54 in thylakoid membrane protein transport, we generatedArabidopsis thalianacpSRP54 knockout (ffc1-2) lines producing truncated cpSRP54 variants or a GTPase point mutation variant. Phenotypic characterization of the complementation lines demonstrated that the C-terminal tail region of cpSRP54 plays an important role specifically in posttranslational LHCP transport. Furthermore, we show that the GTPase activity of cpSRP54 plays an essential role in the transport pathways for both nuclear-as well as plastid-encoded proteins. In addition, our data revealed that plants expressing cpSRP54 without the C-terminal region exhibit a strongly increased accumulation of a photosystem I assembly intermediate.

Highlight

This study elucidates the important role of the chloroplast SRP subunit, cpSRP54, in the biogenesis of both the LHC antenna and the cores of photosystem I and IIin vivo.
From Bulk to Binding: Decoding the Entry of PET into Hydrolase Binding Pockets
Authors: Jäckering Anna , Göttsch Frederike , Schäffler Moritz , Doerr Mark , Bornscheuer Uwe T. , Wei Ren , Strodel Birgit
Published: April 2024

Plastic-degrading enzymes hold promise for biocatalytic recycling of poly(ethylene terephthalate) (PET), a key synthetic polymer. Despite their potential, the current activity of PET hydrolases is not sufficient for industrial use. To unlock their full potential, a deep mechanistic understanding followed by protein engineering is required. Using cuttingedge molecular dynamics simulations and free energy analysis methods, we uncover the entire pathway from the initial binding of two PET hydrolases – the thermophilic leaf-branch compost cutinase (LCC) and polyester hydrolase 1 (PES-H1) – to an amorphous PET material to a PET chain entering the active site and adopting a hydrolyzable geometry. Our results reveal the initial PET binding and elucidate its non-specific nature driven by electrostatic and hydrophobic forces. Upon PET entry into the active site, we uncover that this process can occur via one of three key pathways and detect barriers to it arising from both PET–PET and PET–enzyme interactions, with specific residues identified byin silicoandin vitromutagenesis. These insights not only advance our understanding of PET degradation mechanisms and pave the way for targeted enzyme enhancement strategies, but also offer an innovative approach applicable to enzyme studies across disciplines.
A guide to plant morphometrics using Gaussian Mixture Models
Authors: Tiburtini Manuel , Scrucca Luca , Peruzzi Lorenzo
Published: April 2024

Plant morphology is crucial in defining and circumscribing the plant diversity around us. Statistically speaking, the study of morphology is done using morphometry, that in the context of plant systematics is used to verify hypotheses of morphological independence between taxa. Nevertheless, methods currently used to analyse morphological data do not match with the conceptual model behind species circumscription on morphological grounds. Here we 1) provide a step-by-step guide to perform linear morphometric analyses in the context of plant systematics and 2) we develop a new conceptual, statistical, and probabilistic framework for analyzing morphometric data using Gaussian Mixture Models (GMMs) in plant taxonomy to compare alternative taxonomic hypotheses.
Association between functional ability, chronic diseases and lifestyle risk factors in older community dwelling adults: protocol for a prospective observational Chinese cohort study
Authors: Wei Xin , Dan Xu , Zulin Dou , Angela Jacques , Josephine Umbella , Yuling Fan , Longsheng Zhang , Haiwen Yang , Hong Cai , Anne-Marie Hill
Published: April 2024

Background

The increasing proportion of the ageing population has become a significant focus for healthcare and social services in many countries worldwide, including China. Impaired physical fitness or the presence of chronic diseases may decrease functional ability and health related quality of life for older adults. The aim of the study is to investigate the association between functional abilities, including motor and cognitive function, with lifestyle risk factors, including activities of daily living (ADL), physical activity falls, frailty, and chronic diseases in older adults living in Guangzhou, China.

Methods

A prospective observational cohort study will be conducted. Older adults aged 60 years and over living in urban Guangzhou, China will be eligible for inclusion. This study will be conducted in a community health service centre in Guangzhou. Inclusion criteria are that older adults can independently ambulate short distances indoors with or without a walking aid and can provide written informed consent. The outcomes are functional ability measured using, i Timed Up and Go test (TUGT), gait speed, handgrip strength and Functional Reach Test (FRT), cognition measured using the Mini-Cog, ADL measured with the Lawton Instrumental Activities of Daily Living Scale (Lawton IADL), HR-QoL measured using the European Quality of Life 5 Dimensions 3 Level Version (EQ5D3L), physical activity, falls history, lifestyle risk factors, anthropometric data, presence of chronic diseases measured by standardized blood tests, and blood pressure. Data collection will be performed by two senior physiotherapists and nurses working in the community centre.

Trial registration

Ethical approval (II2023-155-02) for this study was obtained from the Health Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Chinese Clinical Trial Registry Centre

ChiCTR2300076095.
Evaluation of easy-to-implement anti-stress interventions in a series of N-of-1 trials: Study protocol of the Anti-Stress Intervention Among Physicians Study (ASIP)
Authors: Vetter Valentin Max , Kurth Tobias , Konigorski Stefan
Published: April 2024

Background

Adverse effects of chronically high levels of stress on physical and mental health are well established. In physicians, the effects of elevated stress levels exceed the individual level and include treatment errors and reduced quality of patient-doctor relationships. Breathing and mindfulness-based exercises have been shown to reduce stress and could serve as an immediate and easy-to-implement anti-stress intervention among physicians. Due to the heterogeneity of their effect on stress, we aim to evaluate the intervention effect of performing a short daily breathwork-based or mindfulness-based intervention on the everyday level of perceived stress in physicians in residence in Germany in a series of N-of-1 trials.

Methods

Study participants will choose between two short interventions, box breathing, and one guided more complex mindfulness-based breathing exercise. Each participant subsequently will be randomly allocated to a sequence of 1-week intervention (A) and control (B, everyday life) phases. Each N-of-1 trial consists of two two-week cycles (AB or BA), resulting in a total trial duration of 4 weeks (ABAB or BABA). Perceived levels of stress will be assessed daily via the StudyU App on the participant’s smartphone. Additionally, participants will be asked to complete a questionnaire at baseline and three months after completion of the study that contains questions about basic participant characteristics, lifestyle factors, individual living situations, and validated psychological questionnaires. Intervention effects will be estimated by Bayesian multi-level random effects models on the individual and population level.

Discussion

This study contributes to the development of short-term solutions to reduce work-related stress for physicians in residence. This is expected to benefit the individual and increase the quality of overall healthcare due to a reduction in treatment errors and an increase in the quality of doctor-patient relationships.

Trial Registraion

ClinicalTrials.gov:NCT06368791, first registered April 16, 2024.
Mapping the Brazilian Scientific Diaspora: Migration Patterns of PhDs in Global Mobility
Authors: McManus Concepta , Neto Brenno A. D. , Neves Abilio Afonso Baeta , Schleicher Rafael Tavares , Figueiredo Claudia
Published: April 2024

A scientific diaspora refers to a community of scientists who have emigrated from their home country to work in another nation. This study investigates this phenome in depth the Brazilian context, examining who comprises this diaspora (doctorates, postdocs, lecturers), where they have migrated, and their areas of study. We conducted this examination based on publications by Brazilian doctors who graduated between 2005 and 2021, as well as post-doctorates and students with full doctorate scholarships abroad. These students were identified on the CAPES open data website. The publications of these authors were captured in Scopus and Web of Science. Then those with addresses abroad were analysed in Vosviewer® and using logistic regression (stayed abroad or not), area of knowledge and a decision tree to see the effect of the Brazilian university region, type of institution and scholarship on the decision to migrate. The level of diaspora is approximately 1.7% among all doctorates trained in Brazil, reaching 6.6% in postdoctoral scholars with experience abroad. This suggests that PhDs with advanced training and experience have a higher propensity to emigrate from Brazil. These PhDs predominantly choose to migrate to North America and Western Europe, with a strong preference for careers in Science, Technology, Engineering, and Mathematics (STEM) fields. Brazilian PhDs with international experience tend to have a more diverse migration pattern, while those who complete their PhD in Brazil show a distinct preference for migrating to Portugal, indicating differing global mobility based on scientific experience. A decision tree analysis reveals that life or exact sciences PhDs, those who graduated after 2012, and obtained their postgraduate degrees from institutions in the southeast or south of Brazil are more likely to migrate. While the reasons behind these migration patterns are not evaluated in this study, better job prospects, higher salaries, or more substantial research funding could be influential factors in the decision to migrate.
Many-body theory calculations of positron binding to halogenated hydrocarbons
Authors: Cassidy J. P. , Hofierka J. , Cunningham B. , Rawlins C. M. , Patterson C. H. , Green D. G.
Published: April 2024

Positron binding energies in halogenated hydrocarbons are calculated using many-body theory. For chlorinated molecules, including planars for which the interaction is highly anisotropic, very good to excellent agreement with experiment and recent density-functional-theory-based model-potential calculations is found. Predictions for fluorinated and brominated molecules are presented. The comparative effect of fluorination, chlorination, and bromination is elucidated by identifying trends within molecular families including dihaloethylenes and halomethanes based on global molecular properties (dipole moment, polarizability, ionization energy). It is shown that relative to brominated and chlorinated molecules, fluorinated molecules generate a less attractive positron-molecule potential due to larger ionization energies and smaller density of molecular orbitals close to the highest occupied molecular orbital, resulting in very weak, or in most cases loss of, positron binding. Overall, however, it is shown that the global molecular properties are not universal predictors of binding energies, exemplified by consideration of CH3Cl vs -C2H2F2: Despite the latter having a larger dipole moment, lower ionization energy, and similar polarizability, its binding energy is significantly smaller (25 vs 3 meV, respectively), owing to the important contribution of multiple molecular orbitals to, and the anisotropy of, the positron-molecule correlation potential.

Published by the American Physical Society
2024
High repetition rate coherent terahertz synchrotron radiation via self-amplified energy modulation
Authors: Xu Xiazhen , Zhang Haoran , Guo Zixin , Li Jingya , Zhang Jinming , He Zhigang , He Duohui
Published: April 2024

Coherent terahertz (THz) radiation sources based on a storage ring hold a significant future for generating high average power terahertz radiation, as the electron beam possesses a high revolution frequency. We propose a novel scheme to generate a high repetition rate coherent THz radiation leveraging the energy modulation self-amplification technology. In this scheme, utilizing the interaction of external intensity-modulated laser pulses with the electron beam can lead to a customized manipulation of the electron beam, such as a periodic longitudinal density modulation with a submillimeter scale for coherent THz radiation. Positively, it can propel the repetition rate when the peak power requirement of an external laser system is decreased. Thus, we employ a self-modulation method to enhance the initial weak energy modulation induced by the laser directly. In the meanwhile, the use of self-modulation can bypass the limitation that the bandwidth of a long modulator should be smaller than that of the external wideband laser source, which is necessary to shape the intensity envelope flexibly. The one-dimensional analytical description of electron longitudinal dynamic during the self-modulation process is given, which confirms the effective enhancement of the modulation at THz band. Three-dimensional time-dependent simulation results based on the parameters of Hefei light source-II show that the coherent THz radiation pulses with a repetition rate of 10 kHz can be generated.

Published by the American Physical Society
2024